Balint Balint - Academia.edu (original) (raw)
Papers by Balint Balint
Additional figures with data on ATAC-seq. Figure S1. Differential binding analysis identifies dep... more Additional figures with data on ATAC-seq. Figure S1. Differential binding analysis identifies depot-specific chromatin accessibility in preadipocytes. a) Correlation plot of accessible chromatin regions defined by ATAC-seq from different subjects (Sub1 and Sub2), fat depots (gluteofemoral-GF, abdominal-A), and technical replicates (rep#1 and rep#2). b) Identification of differentially open chromatin regions from GF and abdominal preadipocytes using differential binding analysis (DiffBind). Heat map representation of the abdominal- (n = 7160) and the GF-specific (n = 780) open chromatin regions. Sub = subject, Rep = technical replicate. The pairwise correlation scores were used for hierarchical clustering (p
Additional tables with data on RNA-seq and ATAC-seq list of genes. Table S1. Differentially expre... more Additional tables with data on RNA-seq and ATAC-seq list of genes. Table S1. Differentially expressed genes between abdominal and GF depot in subject 1, subject 2, and in both. Table S2. List of open chromatin regions in the proximity of the depot-specific genes. (ZIP 231 kb)
Additional figure with data on PPIA gene expression. Representation of the individual PPIA gene C... more Additional figure with data on PPIA gene expression. Representation of the individual PPIA gene Ct value obtained by RT-qPCR in cells (white squares) and tissue (black squares). A = abdominal depot, G = GF depot. (PPTX 51 kb)
Clinical Epigenetics, 2018
Biochimica et biophysica acta. Molecular and cell biology of lipids, Jan 2, 2018
There is a growing body of evidence that poly(ADP-ribose) polymerase-2 (PARP2), although original... more There is a growing body of evidence that poly(ADP-ribose) polymerase-2 (PARP2), although originally described as a DNA repair protein, has a widespread role as a metabolic regulator. We show that the ablation of PARP2 induced characteristic changes in the lipidome. The silencing of PARP2 induced the expression of sterol regulatory element-binding protein-1 and -2 and initiated de novo cholesterol biosynthesis in skeletal muscle. Increased muscular cholesterol was shunted to muscular biosynthesis of dihydrotestosterone, an anabolic steroid. Thus, skeletal muscle fibers in PARP2 mice were stronger compared to those of their wild-type littermates. In addition, we detected changes in the dynamics of the cell membrane, suggesting that lipidome changes also affect the biophysical characteristics of the cell membrane. In in silico and wet chemistry studies, we identified lipid species that can decrease the expression of PARP2 and potentially phenocopy the genetic abruption of PARP2, includ...
Oncotarget, Jan 31, 2018
Biobanks operating at ambient temperatures would dramatically reduce the costs associated with st... more Biobanks operating at ambient temperatures would dramatically reduce the costs associated with standard cryogenic storage. In the present study, we used lyophilization to stabilize unfractionated human cells in a dried state at room temperature and tested the yield and integrity of the isolated RNA by microfluidic electrophoresis, RT-qPCR and RNA sequencing. RNA yields and integrity measures were not reduced for lyophilized cells (unstored, stored for two weeks or stored for two months) compared to their paired controls. The abundance of the selected mRNAs with various expression levels, as well as enhancer-associated RNAs and cancer biomarker long non-coding RNAs (, and ), were not significantly different between the two groups as assessed by RT-qPCR. RNA sequencing data of three lyophilized samples stored for two weeks at room temperature revealed a high degree of similarity with their paired controls in terms of the RNA biotype distribution, cumulative gene diversity, gene body r...
Immunotherapy, Nov 1, 2017
During the last decades, the prevalence of allergy has dramatically increased. Allergen-specific ... more During the last decades, the prevalence of allergy has dramatically increased. Allergen-specific immunotherapy is the only currently available medical intervention that has the potential to affect the natural course of the disease, but there are still many questions and unmet needs hindering its widespread use to fulfill its treatment potential and maximize its benefits for the society. To provide a comprehensive phenome-wide overview in sublingual immunotherapy, using ragweed allergy as a target, we planned and carried out a longitudinal, prospective, observational, open-label study (DesensIT). In this paper we present challenges of using deep and comprehensive phenotypes embracing biological, clinical and patient-reported outcomes in allergen-specific immunotherapy and show how we designed the DesensIT project to optimize data collection, processing and evaluation.
Nucleic acids research, Jan 20, 2017
Super-enhancers are established through the interactions of several enhancers and a large number ... more Super-enhancers are established through the interactions of several enhancers and a large number of proteins, including transcription factors and co-regulators; however, the formation of these interactions is poorly understood. By re-analysing previously published estrogen receptor alpha (ERα) ChIP-seq data sets derived from the MCF-7 cell line, we observed that in the absence of stimulation, future super-enhancers are represented by one or a few transcription factor binding event(s) and these extraordinary enhancers possess a response element largely specific to the ERα dimer. Upon hormonal stimulation, these primary binding sites are surrounded by a large amount of ERα and the critical components of active enhancers, such as P300 and MED1, and together with neighbouring sites bound by newly recruited ERα, they generate the functional super-enhancers. To further validate the role of canonical elements in super-enhancer formation, we investigated some additional signal-dependent tra...
Pathology oncology research : POR, Jan 18, 2016
Disruption of epigenetic regulation and characteristic metabolic alterations (known as the Warbur... more Disruption of epigenetic regulation and characteristic metabolic alterations (known as the Warburg-effect) are well-known hallmarks of cancer. In our study we investigated the expression levels of microRNAs and histone deacetylase enzymes via RT-qPCR in bone marrow specimens of adult patients suffering from hematological malignancies (total cohort n = 40), especially acute myeloid leukemia (n = 27). The levels of the three examined Warburg-effect related microRNAs (miR-378*, miR-23b, miR-26a) positively correlated with each other and the oncogenic miR-155 and miR-125b, while negatively with the level of the tumorsuppressor miR-124. Significant relationships have been confirmed between the levels of SIRT6, HDAC4 and the microRNAs listed above. In NPM1-mutated AML (n = 6), the level of miR-125b was significantly lower than in the group of AML patients not carrying this mutation (n = 13) (p < 0.05). In M5 FAB type of AML (n = 5), the level of miR-124 was significantly higher compare...
The Journal of Biological Chemistry, Aug 18, 2006
![Research paper thumbnail of [The place of functional genomics in oncological research]](https://attachments.academia-assets.com/84475624/thumbnails/1.jpg)
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A kutatomunka soran szisztematikusan felterkepeztuk az un RXR heterodimer tipusu receptorok szere... more A kutatomunka soran szisztematikusan felterkepeztuk az un RXR heterodimer tipusu receptorok szerepet a human monocita eredetű dendritikus sejtek differencialodasa es immunfunkcioi soran. Ezek a receptorok a PPARg, LXR, VDR es RAR receptorok volta, melyeket kiegeszitettunk az RXR receptorral is. A specikus utvonalak azonositasa mellett altalanos megallapitaskent elmondhattuk, hogy ez a receptorcsalad olyan molekularis szenzorkent műkodik, mely kepes atprogramozni a sejt genkifejeződeset kulső es belső lipid szintek valtozasa soran. Osszefuggest talaltunk az IL4 STAT6-on kerestuli szignalizacioja es a PPARg receptor kozott es legujabban felterkepeztuk a az RXR receptor genomi kotőhelyeit ls cisztromikus kolcsonhatasait is. | During our work we have systematically mapped the so called RXR heterodimeric receptors roles in monocyte derived dendritic cells during differentiation and immune function. These receptors included PPARg, LXR, VDR and RXR and also included their heterodimeric partner RXR. Based on the data obtained one can conclude that besides the specialized pathways identified, these receptors act as molecular sensors in detecting changing extra and intracellular lipid levels. We have also identified an interaction between IL4 mediated STAT6 signaling and PPARg and most recently we have detrained the RXR cistrome and its interactions.
Methods in molecular biology (Clifton, N.J.), 2014
Chromatin immunoprecipitation followed by massively parallel sequencing (ChIP-Seq) is a powerful ... more Chromatin immunoprecipitation followed by massively parallel sequencing (ChIP-Seq) is a powerful technique to map the genomic location of a given chromatin bound factor (i.e., transcription factors, cofactors) or epigenetic marks, such as histone modification. The procedure is based on cross-linking of proteins to DNA followed by the capture of the protein-DNA complexes by "ChIP-grade" antibodies. In this chapter we describe in detail the experimental method developed in our laboratory to investigate in vivo the DNA-binding characteristics of a key heterodimeric nuclear receptor, the retinoid X receptor (RXR) in murine bone marrow-derived macrophages.
STEM CELLS, 2015
Retinoids are morphogens and have been implicated in cell fate commitment of embryonic stem cells... more Retinoids are morphogens and have been implicated in cell fate commitment of embryonic stem cells (ESCs) to neurons. Their effects are mediated by RAR and RXR nuclear receptors. However, transcriptional cofactors required for cell and gene-specific retinoid signaling are not known. Here we show that protein arginine methyl transferase (PRMT) 1 and 8 have key roles in determining retinoid regulated gene expression and cellular specification in a multistage neuronal differentiation model of murine ESCs. PRMT1 acts as a selective modulator, providing the cells with a mechanism to reduce the potency of retinoid signals on regulatory “hotspots.” PRMT8 is a retinoid receptor target gene itself and acts as a cell type specific transcriptional coactivator of retinoid signaling at later stages of differentiation. Lack of either of them leads to reduced nuclear arginine methylation, dysregulated neuronal gene expression, and altered neuronal activity. Importantly, depletion of PRMT8 results i...
PLoS ONE, 2013
Short regulatory RNA-s have been identified as key regulators of gene expression in eukaryotes. T... more Short regulatory RNA-s have been identified as key regulators of gene expression in eukaryotes. They have been involved in the regulation of both physiological and pathological processes such as embryonal development, immunoregulation and cancer. One of their relevant characteristics is their high stability, which makes them excellent candidates for use as biomarkers. Their number is constantly increasing as next generation sequencing methods reveal more and more details of their synthesis. These novel findings aim for new detection methods for the individual short regulatory RNA-s in order to be able to confirm the primary data and characterize newly identified subtypes in different biological conditions. We have developed a flexible method to design RT-qPCR assays that are very sensitive and robust. The newly designed assays were tested extensively in samples from plant, mouse and even human formalin fixed paraffin embedded tissues. Moreover, we have shown that these assays are able to quantify endogenously generated shRNA molecules. The assay design method is freely available for anyone who wishes to use a robust and flexible system for the quantitative analysis of matured regulatory RNA-s.
Additional figures with data on ATAC-seq. Figure S1. Differential binding analysis identifies dep... more Additional figures with data on ATAC-seq. Figure S1. Differential binding analysis identifies depot-specific chromatin accessibility in preadipocytes. a) Correlation plot of accessible chromatin regions defined by ATAC-seq from different subjects (Sub1 and Sub2), fat depots (gluteofemoral-GF, abdominal-A), and technical replicates (rep#1 and rep#2). b) Identification of differentially open chromatin regions from GF and abdominal preadipocytes using differential binding analysis (DiffBind). Heat map representation of the abdominal- (n = 7160) and the GF-specific (n = 780) open chromatin regions. Sub = subject, Rep = technical replicate. The pairwise correlation scores were used for hierarchical clustering (p
Additional tables with data on RNA-seq and ATAC-seq list of genes. Table S1. Differentially expre... more Additional tables with data on RNA-seq and ATAC-seq list of genes. Table S1. Differentially expressed genes between abdominal and GF depot in subject 1, subject 2, and in both. Table S2. List of open chromatin regions in the proximity of the depot-specific genes. (ZIP 231 kb)
Additional figure with data on PPIA gene expression. Representation of the individual PPIA gene C... more Additional figure with data on PPIA gene expression. Representation of the individual PPIA gene Ct value obtained by RT-qPCR in cells (white squares) and tissue (black squares). A = abdominal depot, G = GF depot. (PPTX 51 kb)
Clinical Epigenetics, 2018
Biochimica et biophysica acta. Molecular and cell biology of lipids, Jan 2, 2018
There is a growing body of evidence that poly(ADP-ribose) polymerase-2 (PARP2), although original... more There is a growing body of evidence that poly(ADP-ribose) polymerase-2 (PARP2), although originally described as a DNA repair protein, has a widespread role as a metabolic regulator. We show that the ablation of PARP2 induced characteristic changes in the lipidome. The silencing of PARP2 induced the expression of sterol regulatory element-binding protein-1 and -2 and initiated de novo cholesterol biosynthesis in skeletal muscle. Increased muscular cholesterol was shunted to muscular biosynthesis of dihydrotestosterone, an anabolic steroid. Thus, skeletal muscle fibers in PARP2 mice were stronger compared to those of their wild-type littermates. In addition, we detected changes in the dynamics of the cell membrane, suggesting that lipidome changes also affect the biophysical characteristics of the cell membrane. In in silico and wet chemistry studies, we identified lipid species that can decrease the expression of PARP2 and potentially phenocopy the genetic abruption of PARP2, includ...
Oncotarget, Jan 31, 2018
Biobanks operating at ambient temperatures would dramatically reduce the costs associated with st... more Biobanks operating at ambient temperatures would dramatically reduce the costs associated with standard cryogenic storage. In the present study, we used lyophilization to stabilize unfractionated human cells in a dried state at room temperature and tested the yield and integrity of the isolated RNA by microfluidic electrophoresis, RT-qPCR and RNA sequencing. RNA yields and integrity measures were not reduced for lyophilized cells (unstored, stored for two weeks or stored for two months) compared to their paired controls. The abundance of the selected mRNAs with various expression levels, as well as enhancer-associated RNAs and cancer biomarker long non-coding RNAs (, and ), were not significantly different between the two groups as assessed by RT-qPCR. RNA sequencing data of three lyophilized samples stored for two weeks at room temperature revealed a high degree of similarity with their paired controls in terms of the RNA biotype distribution, cumulative gene diversity, gene body r...
Immunotherapy, Nov 1, 2017
During the last decades, the prevalence of allergy has dramatically increased. Allergen-specific ... more During the last decades, the prevalence of allergy has dramatically increased. Allergen-specific immunotherapy is the only currently available medical intervention that has the potential to affect the natural course of the disease, but there are still many questions and unmet needs hindering its widespread use to fulfill its treatment potential and maximize its benefits for the society. To provide a comprehensive phenome-wide overview in sublingual immunotherapy, using ragweed allergy as a target, we planned and carried out a longitudinal, prospective, observational, open-label study (DesensIT). In this paper we present challenges of using deep and comprehensive phenotypes embracing biological, clinical and patient-reported outcomes in allergen-specific immunotherapy and show how we designed the DesensIT project to optimize data collection, processing and evaluation.
Nucleic acids research, Jan 20, 2017
Super-enhancers are established through the interactions of several enhancers and a large number ... more Super-enhancers are established through the interactions of several enhancers and a large number of proteins, including transcription factors and co-regulators; however, the formation of these interactions is poorly understood. By re-analysing previously published estrogen receptor alpha (ERα) ChIP-seq data sets derived from the MCF-7 cell line, we observed that in the absence of stimulation, future super-enhancers are represented by one or a few transcription factor binding event(s) and these extraordinary enhancers possess a response element largely specific to the ERα dimer. Upon hormonal stimulation, these primary binding sites are surrounded by a large amount of ERα and the critical components of active enhancers, such as P300 and MED1, and together with neighbouring sites bound by newly recruited ERα, they generate the functional super-enhancers. To further validate the role of canonical elements in super-enhancer formation, we investigated some additional signal-dependent tra...
Pathology oncology research : POR, Jan 18, 2016
Disruption of epigenetic regulation and characteristic metabolic alterations (known as the Warbur... more Disruption of epigenetic regulation and characteristic metabolic alterations (known as the Warburg-effect) are well-known hallmarks of cancer. In our study we investigated the expression levels of microRNAs and histone deacetylase enzymes via RT-qPCR in bone marrow specimens of adult patients suffering from hematological malignancies (total cohort n = 40), especially acute myeloid leukemia (n = 27). The levels of the three examined Warburg-effect related microRNAs (miR-378*, miR-23b, miR-26a) positively correlated with each other and the oncogenic miR-155 and miR-125b, while negatively with the level of the tumorsuppressor miR-124. Significant relationships have been confirmed between the levels of SIRT6, HDAC4 and the microRNAs listed above. In NPM1-mutated AML (n = 6), the level of miR-125b was significantly lower than in the group of AML patients not carrying this mutation (n = 13) (p < 0.05). In M5 FAB type of AML (n = 5), the level of miR-124 was significantly higher compare...
The Journal of Biological Chemistry, Aug 18, 2006
A kutatomunka soran szisztematikusan felterkepeztuk az un RXR heterodimer tipusu receptorok szere... more A kutatomunka soran szisztematikusan felterkepeztuk az un RXR heterodimer tipusu receptorok szerepet a human monocita eredetű dendritikus sejtek differencialodasa es immunfunkcioi soran. Ezek a receptorok a PPARg, LXR, VDR es RAR receptorok volta, melyeket kiegeszitettunk az RXR receptorral is. A specikus utvonalak azonositasa mellett altalanos megallapitaskent elmondhattuk, hogy ez a receptorcsalad olyan molekularis szenzorkent műkodik, mely kepes atprogramozni a sejt genkifejeződeset kulső es belső lipid szintek valtozasa soran. Osszefuggest talaltunk az IL4 STAT6-on kerestuli szignalizacioja es a PPARg receptor kozott es legujabban felterkepeztuk a az RXR receptor genomi kotőhelyeit ls cisztromikus kolcsonhatasait is. | During our work we have systematically mapped the so called RXR heterodimeric receptors roles in monocyte derived dendritic cells during differentiation and immune function. These receptors included PPARg, LXR, VDR and RXR and also included their heterodimeric partner RXR. Based on the data obtained one can conclude that besides the specialized pathways identified, these receptors act as molecular sensors in detecting changing extra and intracellular lipid levels. We have also identified an interaction between IL4 mediated STAT6 signaling and PPARg and most recently we have detrained the RXR cistrome and its interactions.
Methods in molecular biology (Clifton, N.J.), 2014
Chromatin immunoprecipitation followed by massively parallel sequencing (ChIP-Seq) is a powerful ... more Chromatin immunoprecipitation followed by massively parallel sequencing (ChIP-Seq) is a powerful technique to map the genomic location of a given chromatin bound factor (i.e., transcription factors, cofactors) or epigenetic marks, such as histone modification. The procedure is based on cross-linking of proteins to DNA followed by the capture of the protein-DNA complexes by "ChIP-grade" antibodies. In this chapter we describe in detail the experimental method developed in our laboratory to investigate in vivo the DNA-binding characteristics of a key heterodimeric nuclear receptor, the retinoid X receptor (RXR) in murine bone marrow-derived macrophages.
STEM CELLS, 2015
Retinoids are morphogens and have been implicated in cell fate commitment of embryonic stem cells... more Retinoids are morphogens and have been implicated in cell fate commitment of embryonic stem cells (ESCs) to neurons. Their effects are mediated by RAR and RXR nuclear receptors. However, transcriptional cofactors required for cell and gene-specific retinoid signaling are not known. Here we show that protein arginine methyl transferase (PRMT) 1 and 8 have key roles in determining retinoid regulated gene expression and cellular specification in a multistage neuronal differentiation model of murine ESCs. PRMT1 acts as a selective modulator, providing the cells with a mechanism to reduce the potency of retinoid signals on regulatory “hotspots.” PRMT8 is a retinoid receptor target gene itself and acts as a cell type specific transcriptional coactivator of retinoid signaling at later stages of differentiation. Lack of either of them leads to reduced nuclear arginine methylation, dysregulated neuronal gene expression, and altered neuronal activity. Importantly, depletion of PRMT8 results i...
PLoS ONE, 2013
Short regulatory RNA-s have been identified as key regulators of gene expression in eukaryotes. T... more Short regulatory RNA-s have been identified as key regulators of gene expression in eukaryotes. They have been involved in the regulation of both physiological and pathological processes such as embryonal development, immunoregulation and cancer. One of their relevant characteristics is their high stability, which makes them excellent candidates for use as biomarkers. Their number is constantly increasing as next generation sequencing methods reveal more and more details of their synthesis. These novel findings aim for new detection methods for the individual short regulatory RNA-s in order to be able to confirm the primary data and characterize newly identified subtypes in different biological conditions. We have developed a flexible method to design RT-qPCR assays that are very sensitive and robust. The newly designed assays were tested extensively in samples from plant, mouse and even human formalin fixed paraffin embedded tissues. Moreover, we have shown that these assays are able to quantify endogenously generated shRNA molecules. The assay design method is freely available for anyone who wishes to use a robust and flexible system for the quantitative analysis of matured regulatory RNA-s.