Ronald Berezney - Academia.edu (original) (raw)

Papers by Ronald Berezney

Academic Press eBooks, 1995

... Slater Instituut, University of Amsterdam, 1018 TV Amsterdam, The Netherlands Xiangyun Wei (1... more ... Slater Instituut, University of Amsterdam, 1018 TV Amsterdam, The Netherlands Xiangyun Wei (1A), Department of Biological Sciences, State University of New York at Buffalo, Buffalo, New York 14260 C. Zeng (1B), Verna and Marrs McLean Department of Biochemistry, Baylor ...

International review of cytology, 1996

While significant progress has been made in elucidating molecular properties of specific genes an... more While significant progress has been made in elucidating molecular properties of specific genes and their regulation, our understanding of how the whole genome is coordinated has lagged behind. To understand how the genome functions as a coordinated whole, we must understand how the nucleus is put together and functions as a whole. An important step in that direction occurred with the isolation and characterization of the nuclear matrix. Aside from the plethora of functional properties associated with these isolated nuclear structures, they have enabled the first direct examination and molecular cloning of specific nuclear matrix proteins. The isolated nuclear matrix can be used for providing an in vitro model for understanding nuclear matrix organization in whole cells. Recent development of high-resolution and three-dimensional approaches for visualizing domains of genomic organization and function in situ has provided corroborative evidence for the nuclear matrix as the site of organization for replication, transcription, and post-transcriptional processing. As more is learned about these in situ functional sites, appropriate experiments could be designed to test molecular mechanisms with the in vitro nuclear matrix systems. This is illustrated in this chapter by the studies of nuclear matrix-associated DNA replication which have evolved from biochemical studies of in vitro nuclear matrix systems toward three-dimensional computer image analysis of replication sites for individual genes.

Lecture Notes in Computer Science, 2006

Recent research in biology has indicated correlations between the movement patterns of functional... more Recent research in biology has indicated correlations between the movement patterns of functional sites (such as replication sites in DNA) and zones of genetic activity within a nucleus. A detailed study and analysis of the motion dynamics of these sites can reveal an interesting insight into their role in DNA replication and function. In this paper, we propose a suite of novel techniques to determine, analyze, and interpret the mobility patterns of functional sites. Our algorithms are based on interesting ideas from theoretical computer science and database theory and provide for the first time the tools to interpret the seemingly stochastic motion patterns of the functional sites within the nucleus in terms of a set of tractable 'patterns' which can then be analyzed to understand their biological significance.

Proceedings of the National Academy of Sciences of the United States of America, Jul 15, 1991

Computing accurate and robust organizational patterns of chromosome territories inside the cell n... more Computing accurate and robust organizational patterns of chromosome territories inside the cell nucleus is critical for understanding several fundamental genomic processes, such as co-regulation of gene activation, gene silencing, X chromosome inactivation, and abnormal chromosome rearrangement in cancer cells. The usage of advanced fluorescence labeling and image processing techniques has enabled researchers to investigate interactions of chromosome territories at large spatial resolution. The resulting high volume of generated data demands for high-throughput and automated image analysis methods. In this paper, we introduce a novel algorithmic tool for investigating association patterns of chromosome territories in a population of cells. Our method takes as input a set of graphs, one for each cell, containing information about spatial interaction of chromosome territories, and yields a single graph that contains essential information for the whole population and stands as its structural representative. We formulate this combinatorial problem as a semi-definite programming and present novel techniques to efficiently solve it. We validate our approach on both artificial and real biological data; the experimental results suggest that our approach yields a nearoptimal solution, and can handle large-size datasets, which are significant improvements over existing techniques.

Chromosoma, Aug 9, 2014

Despite decades of study of chromosome territories (CT) in the interphase nucleus of mammalian ce... more Despite decades of study of chromosome territories (CT) in the interphase nucleus of mammalian cells, our understanding of the global shape and 3-D organization of the individual CT remains very limited. Past microscopic analysis of CT suggested that, while many of the CT appear to be very regular ellipsoid-like shapes, there were also those with more irregular shapes. We have undertaken a comprehensive analysis to determine the degree of shape regularity of different CT. To be representative of the whole human genome, 12 different CT (~41% of the genome) were selected that ranged from the largest (CT 1) to the smallest (CT 21) in size and from the highest (CT 19) to lowest (CT Y) in gene density. Using both visual inspection and algorithms that measure the degree of shape ellipticity and regularity, we demonstrate a strong inverse correlation between the degree of regular CT shape and gene density for those CT that are most gene rich (19, 17, 11) and gene poor (18, 13, Y). CT more intermediate in gene density, showed a strong negative correlation with shape regularity but not with ellipticity. An even more striking correlation between gene density and CT shape was determined for the nucleolar associated NOR-CT. Correspondingly striking differences in shape between the X active and inactive CT implied that, aside from gene density, the overall global level of gene transcription on individual CT is also an important determinant of chromosome territory shape.

Journal of Cell Biology, Jun 1, 1980

Isolated rat liver nuclear matrices have been partially separated by means of mild sonication int... more Isolated rat liver nuclear matrices have been partially separated by means of mild sonication into a matrix protein (matricin) fraction and a residual ribonucleoprotein (RNP) fraction . The initial matricin fraction is composed largely of protein (91 .1%) but also contains significant amounts of DNA (8.4%) . Reconstruction experiments indicate that this DNA is not the result of the artifactual binding of DNA to the matrix during the extraction procedures. Subsequent treatment with DNase I results in purified matricin composed of >99 .5% protein. SDS acrylamide gel electrophoresis of the matrix protein fibrils reveals only three bands: the primary matrix polypeptides of 62,000, 66,000, and 70,000 daltons. Electron microscopy demonstrates a diffuse reticulum with fibrils as thin as 30-50 A and the presence of 80-100-A globular structures . The residual RNP fraction is composed largely of protein (80 .1%) and RNA (19 .5%), with only traces of DNA (1 .I%) . Over 98% of the total matrix-associated RNA is recovered in this fraction . SDS acrylamide gel electrophoresis indicates an enrichment in both low and high molecular weight secondary matrix polypeptides, although the 60,000-70,000dalton polypeptides are present in significant amounts as well . Ultrastructural analysis of the residual RNP fraction reveals distinct electron-dense-staining matrix particles (150-350 A) attached to a fibrous matricin network.

Journal of Cell Biology, Jun 1, 1977

We study the so-called Generalized Median graph problem where the task is to to construct a proto... more We study the so-called Generalized Median graph problem where the task is to to construct a prototype (i.e., a 'model') from an input set of graphs. The problem finds applications in many vision (e.g., object recognition) and learning problems where graphs are increasingly being adopted as a representation tool. Existing techniques for this problem are evolutionary search based; in this paper, we propose a polynomial time algorithm based on a linear programming formulation. We present an additional bi-level method to obtain solutions arbitrarily close to the optimal in non-polynomial time (in worst case). Within this new framework, one can optimize edit distance functions that capture similarity by considering vertex labels as well as the graph structure simultaneously. In context of our motivating application, we discuss experiments on molecular image analysis problems -the methods will provide the basis for building a topological map of all pairs of the human chromosome.

Neural Information Processing Systems, Dec 5, 2013

In this paper, we study the following new variant of prototype learning, called k-prototype learn... more In this paper, we study the following new variant of prototype learning, called k-prototype learning problem for 3D rigid structures: Given a set of 3D rigid structures, find a set of k rigid structures so that each of them is a prototype for a cluster of the given rigid structures and the total cost (or dissimilarity) is minimized. Prototype learning is a core problem in machine learning and has a wide range of applications in many areas. Existing results on this problem have mainly focused on the graph domain. In this paper, we present the first algorithm for learning multiple prototypes from 3D rigid structures. Our result is based on a number of new insights to rigid structures alignment, clustering, and prototype reconstruction, and is practically efficient with quality guarantee. We validate our approach using two type of data sets, random data and biological data of chromosome territories. Experiments suggest that our approach can effectively learn prototypes in both types of data.

Chromosoma, Oct 21, 2015

The well-established human epidermal keratinocyte (HEK) differentiation model was investigated to... more The well-established human epidermal keratinocyte (HEK) differentiation model was investigated to determine possible alterations in chromosome territory (CT) association during differentiation. The seven human chromosomes (1, 4, 11, 12, 16, 17, and 18) selected for this analysis are representative of the chromosome size and gene density range of the overall human genome as well as including a majority of genes involved in epidermal development and differentiation (CT1, 12, and 17). Induction with calcium chloride (Ca(2+)) resulted in morphological changes characteristic of keratinocyte differentiation. Combined multi-fluorescence in situ hybridization (FISH) and computational image analysis on the undifferentiated (0 h) and differentiated (24 h after Ca(2+) treatment) HEK revealed that (a) increases in CT volumes correspond to overall nuclear volume increases, (b) radial positioning is gene density-dependent at 0 h but neither gene density- nor size-dependent at 24 h, (c) the average number of interchromosomal associations for each CT is gene density-dependent and similar at both time points, and (d) there are striking differences in the single and multiple pairwise interchromosomal association profiles. Probabilistic network models of the overall interchromosomal associations demonstrate major reorganization of the network during differentiation. Only ~40 % of the CT pairwise connections in the networks are common to both 0 and 24 h HEK. We propose that there is a probabilistic chromosome positional code which can be significantly altered during cell differentiation in coordination with reprogramming of gene expression.

Journal of Cell Science, Mar 1, 1991

Different agents have been employed to extract the histories and other soluble components from is... more Different agents have been employed to extract the histories and other soluble components from isolated HeLa S3 nuclei during nuclear matrix isolation. We report that 0.2 M (NH4) 2 SO 4 is a milder extracting agent than NaCl and LJS (lithium 3,5-diiodosalicylate), on the basis of the apparent preservation of the elaborate fibrogranular network and the residual nucleolus that resemble the in situ structures in whole cells and nuclei, minimal aggregation, and sufficient solubilization of DNA and histories. The importance of intermolecular disulfide bonds, RNA and 37 °C stabilization on the structural integrity of the nuclear matrix was examined in detail using sulfydryl alkylating, reducing and oxidizing agents, and RNase A. The data suggest that any disulfides formed during the isolation are not essential for maintaining the structural integrity of the in vitro matrix. However, structural integrity of the matrix is dependent upon RNA and to some degree on disulfides that presumably existed in situ. Sodium tetrathionate and 37 °C stabilization of isolated nuclei resulted in nuclear matrices containing an approximately twofold greater amount of protein, RNA and DNA than control preparations. The 37 °C incubation, unlike the sodium tetrathionate stabilization, does not appear to induce intermolecular disulfide bond formation. Neither stabilizations resulted in significant differences of the major matrix polypeptide pattern on two-dimensional (2-D) gels stained with Coomassie Blue as compared to that of unstabilized matrix. The major nuclear matrix proteins, other than the lamins, did not react to the Pruss murine monoclonal antibody (IFA) that recognizes all known intermediate filament proteins, suggesting that the internal matrix proteins are not related to the lamins in intermediate filament-like quality.

Journal of Cellular Biochemistry, Oct 1, 1991

Science, Sep 4, 1998

Microscopy shows that individual sites of DNA replication and transcription of mammalian nuclei s... more Microscopy shows that individual sites of DNA replication and transcription of mammalian nuclei segregate into sets of roughly 22 and 16 higher order domains, respectively. Each domain set displayed a distinct network-like appearance, including regions of individual domains and interdigitation of domains between the two networks. These data support a dynamic mosaic model for the higher order arrangement of genomic function inside the cell nuclei.

Springer eBooks, 2005

Current techniques for microscopic imaging do not provide necessary spatial and temporal resoluti... more Current techniques for microscopic imaging do not provide necessary spatial and temporal resolutions for real time visualization of the nucleus. Images can only be acquired in time lapse mode, leading to significant loss of information between image frames. Such data, if available, can be extremely helpful in the study of nuclear organization and function. In this paper, we present a gamut of geometric-technique-based approaches for solving the problem. Our techniques, working together, can effectively recover complicated motion and deformation as well as the change of intensity surfaces from pairs of images in a microscopic image sequence, and has low time complexity, particularly desirable by many biological applications where large amount of DNA need to be processed. These techniques are also readily applicable to other types of images for reconstructing motion and intensity surfaces of deformable objects.

Cancer Research, Jul 15, 2009

Molecular and Cellular Biology, Apr 1, 1998

Yeast two-hybrid screening has led to the identification of a family of proteins that interact wi... more Yeast two-hybrid screening has led to the identification of a family of proteins that interact with the repetitive C-terminal repeat domain (CTD) of RNA polymerase II (A. Yuryev et al., Proc. Natl. Acad. Sci. USA 93:6975-6980, 1996). In addition to serine/arginine-rich SR motifs, the SCAFs (SR-like CTD-associated factors) contain discrete CTD-interacting domains. In this paper, we show that the CTD-interacting domain of SCAF8 specifically binds CTD molecules phosphorylated on serines 2 and 5 of the consensus sequence Tyr 1 Ser 2 Pro 3 Thr 4 Ser 5 Pro 6 Ser 7 . In addition, we demonstrate that SCAF8 associates with hyperphosphorylated but not with hypophosphorylated RNA polymerase II in vitro and in vivo. This result suggests that SCAF8 is not present in preinitiation complexes but rather associates with elongating RNA polymerase II. Immunolocalization studies show that SCAF8 is present in granular nuclear foci which correspond to sites of active transcription. We also provide evidence that SCAF8 foci are associated with the nuclear matrix. A fraction of these sites overlap with a subset of larger nuclear speckles containing phosphorylated polymerase II. Taken together, our results indicate a possible role for SCAF8 in linking transcription and pre-mRNA processing.

Proceedings of the National Academy of Sciences of the United States of America, Aug 6, 1996

A hyperphosphorylated form of the largest subunit of RNA polymerase II (pol IIo) is associated wi... more A hyperphosphorylated form of the largest subunit of RNA polymerase II (pol IIo) is associated with the pre-mRNA splicing process. Pol IIo was detected in association with a subset of small nuclear ribonucleoprotein particle and Ser-Arg protein splicing factors and also with pre-mRNA splicing complexes assembled in vitro. A subpopulation of pol

Lecture Notes in Computer Science, 2010

Academic Press eBooks, 1995

... Slater Instituut, University of Amsterdam, 1018 TV Amsterdam, The Netherlands Xiangyun Wei (1... more ... Slater Instituut, University of Amsterdam, 1018 TV Amsterdam, The Netherlands Xiangyun Wei (1A), Department of Biological Sciences, State University of New York at Buffalo, Buffalo, New York 14260 C. Zeng (1B), Verna and Marrs McLean Department of Biochemistry, Baylor ...

International review of cytology, 1996

While significant progress has been made in elucidating molecular properties of specific genes an... more While significant progress has been made in elucidating molecular properties of specific genes and their regulation, our understanding of how the whole genome is coordinated has lagged behind. To understand how the genome functions as a coordinated whole, we must understand how the nucleus is put together and functions as a whole. An important step in that direction occurred with the isolation and characterization of the nuclear matrix. Aside from the plethora of functional properties associated with these isolated nuclear structures, they have enabled the first direct examination and molecular cloning of specific nuclear matrix proteins. The isolated nuclear matrix can be used for providing an in vitro model for understanding nuclear matrix organization in whole cells. Recent development of high-resolution and three-dimensional approaches for visualizing domains of genomic organization and function in situ has provided corroborative evidence for the nuclear matrix as the site of organization for replication, transcription, and post-transcriptional processing. As more is learned about these in situ functional sites, appropriate experiments could be designed to test molecular mechanisms with the in vitro nuclear matrix systems. This is illustrated in this chapter by the studies of nuclear matrix-associated DNA replication which have evolved from biochemical studies of in vitro nuclear matrix systems toward three-dimensional computer image analysis of replication sites for individual genes.

Lecture Notes in Computer Science, 2006

Recent research in biology has indicated correlations between the movement patterns of functional... more Recent research in biology has indicated correlations between the movement patterns of functional sites (such as replication sites in DNA) and zones of genetic activity within a nucleus. A detailed study and analysis of the motion dynamics of these sites can reveal an interesting insight into their role in DNA replication and function. In this paper, we propose a suite of novel techniques to determine, analyze, and interpret the mobility patterns of functional sites. Our algorithms are based on interesting ideas from theoretical computer science and database theory and provide for the first time the tools to interpret the seemingly stochastic motion patterns of the functional sites within the nucleus in terms of a set of tractable 'patterns' which can then be analyzed to understand their biological significance.

Proceedings of the National Academy of Sciences of the United States of America, Jul 15, 1991

Computing accurate and robust organizational patterns of chromosome territories inside the cell n... more Computing accurate and robust organizational patterns of chromosome territories inside the cell nucleus is critical for understanding several fundamental genomic processes, such as co-regulation of gene activation, gene silencing, X chromosome inactivation, and abnormal chromosome rearrangement in cancer cells. The usage of advanced fluorescence labeling and image processing techniques has enabled researchers to investigate interactions of chromosome territories at large spatial resolution. The resulting high volume of generated data demands for high-throughput and automated image analysis methods. In this paper, we introduce a novel algorithmic tool for investigating association patterns of chromosome territories in a population of cells. Our method takes as input a set of graphs, one for each cell, containing information about spatial interaction of chromosome territories, and yields a single graph that contains essential information for the whole population and stands as its structural representative. We formulate this combinatorial problem as a semi-definite programming and present novel techniques to efficiently solve it. We validate our approach on both artificial and real biological data; the experimental results suggest that our approach yields a nearoptimal solution, and can handle large-size datasets, which are significant improvements over existing techniques.

Chromosoma, Aug 9, 2014

Despite decades of study of chromosome territories (CT) in the interphase nucleus of mammalian ce... more Despite decades of study of chromosome territories (CT) in the interphase nucleus of mammalian cells, our understanding of the global shape and 3-D organization of the individual CT remains very limited. Past microscopic analysis of CT suggested that, while many of the CT appear to be very regular ellipsoid-like shapes, there were also those with more irregular shapes. We have undertaken a comprehensive analysis to determine the degree of shape regularity of different CT. To be representative of the whole human genome, 12 different CT (~41% of the genome) were selected that ranged from the largest (CT 1) to the smallest (CT 21) in size and from the highest (CT 19) to lowest (CT Y) in gene density. Using both visual inspection and algorithms that measure the degree of shape ellipticity and regularity, we demonstrate a strong inverse correlation between the degree of regular CT shape and gene density for those CT that are most gene rich (19, 17, 11) and gene poor (18, 13, Y). CT more intermediate in gene density, showed a strong negative correlation with shape regularity but not with ellipticity. An even more striking correlation between gene density and CT shape was determined for the nucleolar associated NOR-CT. Correspondingly striking differences in shape between the X active and inactive CT implied that, aside from gene density, the overall global level of gene transcription on individual CT is also an important determinant of chromosome territory shape.

Journal of Cell Biology, Jun 1, 1980

Isolated rat liver nuclear matrices have been partially separated by means of mild sonication int... more Isolated rat liver nuclear matrices have been partially separated by means of mild sonication into a matrix protein (matricin) fraction and a residual ribonucleoprotein (RNP) fraction . The initial matricin fraction is composed largely of protein (91 .1%) but also contains significant amounts of DNA (8.4%) . Reconstruction experiments indicate that this DNA is not the result of the artifactual binding of DNA to the matrix during the extraction procedures. Subsequent treatment with DNase I results in purified matricin composed of >99 .5% protein. SDS acrylamide gel electrophoresis of the matrix protein fibrils reveals only three bands: the primary matrix polypeptides of 62,000, 66,000, and 70,000 daltons. Electron microscopy demonstrates a diffuse reticulum with fibrils as thin as 30-50 A and the presence of 80-100-A globular structures . The residual RNP fraction is composed largely of protein (80 .1%) and RNA (19 .5%), with only traces of DNA (1 .I%) . Over 98% of the total matrix-associated RNA is recovered in this fraction . SDS acrylamide gel electrophoresis indicates an enrichment in both low and high molecular weight secondary matrix polypeptides, although the 60,000-70,000dalton polypeptides are present in significant amounts as well . Ultrastructural analysis of the residual RNP fraction reveals distinct electron-dense-staining matrix particles (150-350 A) attached to a fibrous matricin network.

Journal of Cell Biology, Jun 1, 1977

We study the so-called Generalized Median graph problem where the task is to to construct a proto... more We study the so-called Generalized Median graph problem where the task is to to construct a prototype (i.e., a 'model') from an input set of graphs. The problem finds applications in many vision (e.g., object recognition) and learning problems where graphs are increasingly being adopted as a representation tool. Existing techniques for this problem are evolutionary search based; in this paper, we propose a polynomial time algorithm based on a linear programming formulation. We present an additional bi-level method to obtain solutions arbitrarily close to the optimal in non-polynomial time (in worst case). Within this new framework, one can optimize edit distance functions that capture similarity by considering vertex labels as well as the graph structure simultaneously. In context of our motivating application, we discuss experiments on molecular image analysis problems -the methods will provide the basis for building a topological map of all pairs of the human chromosome.

Neural Information Processing Systems, Dec 5, 2013

In this paper, we study the following new variant of prototype learning, called k-prototype learn... more In this paper, we study the following new variant of prototype learning, called k-prototype learning problem for 3D rigid structures: Given a set of 3D rigid structures, find a set of k rigid structures so that each of them is a prototype for a cluster of the given rigid structures and the total cost (or dissimilarity) is minimized. Prototype learning is a core problem in machine learning and has a wide range of applications in many areas. Existing results on this problem have mainly focused on the graph domain. In this paper, we present the first algorithm for learning multiple prototypes from 3D rigid structures. Our result is based on a number of new insights to rigid structures alignment, clustering, and prototype reconstruction, and is practically efficient with quality guarantee. We validate our approach using two type of data sets, random data and biological data of chromosome territories. Experiments suggest that our approach can effectively learn prototypes in both types of data.

Chromosoma, Oct 21, 2015

The well-established human epidermal keratinocyte (HEK) differentiation model was investigated to... more The well-established human epidermal keratinocyte (HEK) differentiation model was investigated to determine possible alterations in chromosome territory (CT) association during differentiation. The seven human chromosomes (1, 4, 11, 12, 16, 17, and 18) selected for this analysis are representative of the chromosome size and gene density range of the overall human genome as well as including a majority of genes involved in epidermal development and differentiation (CT1, 12, and 17). Induction with calcium chloride (Ca(2+)) resulted in morphological changes characteristic of keratinocyte differentiation. Combined multi-fluorescence in situ hybridization (FISH) and computational image analysis on the undifferentiated (0 h) and differentiated (24 h after Ca(2+) treatment) HEK revealed that (a) increases in CT volumes correspond to overall nuclear volume increases, (b) radial positioning is gene density-dependent at 0 h but neither gene density- nor size-dependent at 24 h, (c) the average number of interchromosomal associations for each CT is gene density-dependent and similar at both time points, and (d) there are striking differences in the single and multiple pairwise interchromosomal association profiles. Probabilistic network models of the overall interchromosomal associations demonstrate major reorganization of the network during differentiation. Only ~40 % of the CT pairwise connections in the networks are common to both 0 and 24 h HEK. We propose that there is a probabilistic chromosome positional code which can be significantly altered during cell differentiation in coordination with reprogramming of gene expression.

Journal of Cell Science, Mar 1, 1991

Different agents have been employed to extract the histories and other soluble components from is... more Different agents have been employed to extract the histories and other soluble components from isolated HeLa S3 nuclei during nuclear matrix isolation. We report that 0.2 M (NH4) 2 SO 4 is a milder extracting agent than NaCl and LJS (lithium 3,5-diiodosalicylate), on the basis of the apparent preservation of the elaborate fibrogranular network and the residual nucleolus that resemble the in situ structures in whole cells and nuclei, minimal aggregation, and sufficient solubilization of DNA and histories. The importance of intermolecular disulfide bonds, RNA and 37 °C stabilization on the structural integrity of the nuclear matrix was examined in detail using sulfydryl alkylating, reducing and oxidizing agents, and RNase A. The data suggest that any disulfides formed during the isolation are not essential for maintaining the structural integrity of the in vitro matrix. However, structural integrity of the matrix is dependent upon RNA and to some degree on disulfides that presumably existed in situ. Sodium tetrathionate and 37 °C stabilization of isolated nuclei resulted in nuclear matrices containing an approximately twofold greater amount of protein, RNA and DNA than control preparations. The 37 °C incubation, unlike the sodium tetrathionate stabilization, does not appear to induce intermolecular disulfide bond formation. Neither stabilizations resulted in significant differences of the major matrix polypeptide pattern on two-dimensional (2-D) gels stained with Coomassie Blue as compared to that of unstabilized matrix. The major nuclear matrix proteins, other than the lamins, did not react to the Pruss murine monoclonal antibody (IFA) that recognizes all known intermediate filament proteins, suggesting that the internal matrix proteins are not related to the lamins in intermediate filament-like quality.

Journal of Cellular Biochemistry, Oct 1, 1991

Science, Sep 4, 1998

Microscopy shows that individual sites of DNA replication and transcription of mammalian nuclei s... more Microscopy shows that individual sites of DNA replication and transcription of mammalian nuclei segregate into sets of roughly 22 and 16 higher order domains, respectively. Each domain set displayed a distinct network-like appearance, including regions of individual domains and interdigitation of domains between the two networks. These data support a dynamic mosaic model for the higher order arrangement of genomic function inside the cell nuclei.

Springer eBooks, 2005

Current techniques for microscopic imaging do not provide necessary spatial and temporal resoluti... more Current techniques for microscopic imaging do not provide necessary spatial and temporal resolutions for real time visualization of the nucleus. Images can only be acquired in time lapse mode, leading to significant loss of information between image frames. Such data, if available, can be extremely helpful in the study of nuclear organization and function. In this paper, we present a gamut of geometric-technique-based approaches for solving the problem. Our techniques, working together, can effectively recover complicated motion and deformation as well as the change of intensity surfaces from pairs of images in a microscopic image sequence, and has low time complexity, particularly desirable by many biological applications where large amount of DNA need to be processed. These techniques are also readily applicable to other types of images for reconstructing motion and intensity surfaces of deformable objects.

Cancer Research, Jul 15, 2009

Molecular and Cellular Biology, Apr 1, 1998

Yeast two-hybrid screening has led to the identification of a family of proteins that interact wi... more Yeast two-hybrid screening has led to the identification of a family of proteins that interact with the repetitive C-terminal repeat domain (CTD) of RNA polymerase II (A. Yuryev et al., Proc. Natl. Acad. Sci. USA 93:6975-6980, 1996). In addition to serine/arginine-rich SR motifs, the SCAFs (SR-like CTD-associated factors) contain discrete CTD-interacting domains. In this paper, we show that the CTD-interacting domain of SCAF8 specifically binds CTD molecules phosphorylated on serines 2 and 5 of the consensus sequence Tyr 1 Ser 2 Pro 3 Thr 4 Ser 5 Pro 6 Ser 7 . In addition, we demonstrate that SCAF8 associates with hyperphosphorylated but not with hypophosphorylated RNA polymerase II in vitro and in vivo. This result suggests that SCAF8 is not present in preinitiation complexes but rather associates with elongating RNA polymerase II. Immunolocalization studies show that SCAF8 is present in granular nuclear foci which correspond to sites of active transcription. We also provide evidence that SCAF8 foci are associated with the nuclear matrix. A fraction of these sites overlap with a subset of larger nuclear speckles containing phosphorylated polymerase II. Taken together, our results indicate a possible role for SCAF8 in linking transcription and pre-mRNA processing.

Proceedings of the National Academy of Sciences of the United States of America, Aug 6, 1996

A hyperphosphorylated form of the largest subunit of RNA polymerase II (pol IIo) is associated wi... more A hyperphosphorylated form of the largest subunit of RNA polymerase II (pol IIo) is associated with the pre-mRNA splicing process. Pol IIo was detected in association with a subset of small nuclear ribonucleoprotein particle and Ser-Arg protein splicing factors and also with pre-mRNA splicing complexes assembled in vitro. A subpopulation of pol

Lecture Notes in Computer Science, 2010