Hyeseon Kang - Academia.edu (original) (raw)

Papers by Hyeseon Kang

Genes & Development, 2020

During mitosis, transcription of genomic DNA is dramatically reduced, before it is reactivated du... more During mitosis, transcription of genomic DNA is dramatically reduced, before it is reactivated during nuclear reformation in anaphase/telophase. Many aspects of the underlying principles that mediate transcriptional memory and reactivation in the daughter cells remain unclear. Here, we used ChIP-seq on synchronized cells at different stages after mitosis to generate genome-wide maps of histone modifications. Combined with EU-RNA-seq and Hi-C analyses, we found that during prometaphase, promoters, enhancers, and insulators retain H3K4me3 and H3K4me1, while losing H3K27ac. Enhancers globally retaining mitotic H3K4me1 or locally retaining mitotic H3K27ac are associated with cell type-specific genes and their transcription factors for rapid transcriptional activation. As cells exit mitosis, promoters regain H3K27ac, which correlates with transcriptional reactivation. Insulators also gain H3K27ac and CCCTC-binding factor (CTCF) in anaphase/telophase. This increase of H3K27ac in anaphase/...

Circulation, Jan 29, 2017

Background -Bone Morphogenetic Protein (BMP) signaling has multiple roles in the development and ... more Background -Bone Morphogenetic Protein (BMP) signaling has multiple roles in the development and function of the blood vessels. In humans, mutations in BMP type 2 receptors (BMPR2), a key component of BMP signaling, have been identified in the majority of patients with familial pulmonary arterial hypertension (PAH). However, only a small subset of individuals with BMPR2 mutation develops PAH, suggesting that additional modifiers of BMPR2 function play an important role in the onset and progression of PAH. Methods -We utilized a combination of studies in zebrafish embryos and genetically engineered mice lacking endothelial expression of Vegfr3 to determine the interaction between VEGFR3 and BMPR2. Additional in vitro studies were performed using human endothelial cells, including primary endothelial cells from subjects with PAH. Results -Attenuation of Vegfr3 in zebrafish embryos abrogated Bmp2b-induced ectopic angiogenesis. Endothelial cells (ECs) with disrupted VEGFR3 expression fa...

Developmental Cell, 2012

Bone morphogenetic proteins (BMPs) have diverse functions during development in vertebrates. We h... more Bone morphogenetic proteins (BMPs) have diverse functions during development in vertebrates. We have recently shown that BMP2 signaling promotes venous-specific angiogenesis in zebrafish embryos. However, factors that confer a context-dependent proangiogenic function of BMP2 signaling within endothelial cells need to be identified. Here, we report that Disabled homolog 2 (Dab2), a cargospecific adaptor protein for Clathrin, is essential to mediate the proangiogenic function of BMP2 signaling. We find that inhibition of Dab2 attenuates internalization of BMP receptors and abrogates the proangiogenic effects of BMP signaling in endothelial cells. Moreover, inhibition of Dab2 decreases phosphorylation of SMAD-1, 5, and 8, indicating that Dab2 plays an essential role in determining the outcome of BMP signaling within endothelial cells and may provide a molecular basis for a contextdependent proangiogenic function of BMP2 signaling.

Arteriosclerosis, Thrombosis, and Vascular Biology, 2013

Objective— Apelin and its cognate receptor Aplnr/Apj are essential for diverse biological process... more Objective— Apelin and its cognate receptor Aplnr/Apj are essential for diverse biological processes. However, the function of Apelin signaling in lymphatic development remains to be identified, despite the preferential expression of Apelin and Aplnr within developing blood and lymphatic endothelial cells in vertebrates. In this report, we aim to delineate the functions of Apelin signaling during lymphatic development. Approach and Results— We investigated the functions of Apelin signaling during lymphatic development using zebrafish embryos and found that attenuation of Apelin signaling substantially decreased the formation of the parachordal vessel and the number of lymphatic endothelial cells within the developing thoracic duct, indicating an essential role of Apelin signaling during the early phase of lymphatic development. Mechanistically, we found that abrogation of Apelin signaling selectively attenuates lymphatic endothelial serine–threonine kinase Akt 1/2 phosphorylation wit...

Dynamic regulation of genome during cell division and at the nuclear periphery

In eukaryotes, the genome is hierarchically packaged inside the nucleus. The 3D organization of c... more In eukaryotes, the genome is hierarchically packaged inside the nucleus. The 3D organization of chromatin regulates various biological processes such as transcription, DNA replication, and cell division. The accurate gene regulation depends on when and where chromosomal interactions take place in the nucleus. This dissertation focuses on how the genome maintains its function after passing through mitosis and how the nuclear architecture at the nuclear periphery modulates transcription regulation.A long-standing question in the field is how cells maintain genome structure and function over multiple cell divisions, despite the loss of, for example, chromatin structure and gene expression during mitosis. In the first part of this dissertation, we determine that retention of histone modification binding contributes to accurate transcriptional programs and genome organization. We characterize the role of H3K27ac in the activation of post-mitotic transcription. An increase in H3K27ac bind...

Genes & Development, 2020

During mitosis, transcription of genomic DNA is dramatically reduced, before it is reactivated du... more During mitosis, transcription of genomic DNA is dramatically reduced, before it is reactivated during nuclear reformation in anaphase/telophase. Many aspects of the underlying principles that mediate transcriptional memory and reactivation in the daughter cells remain unclear. Here, we used ChIP-seq on synchronized cells at different stages after mitosis to generate genome-wide maps of histone modifications. Combined with EU-RNA-seq and Hi-C analyses, we found that during prometaphase, promoters, enhancers, and insulators retain H3K4me3 and H3K4me1, while losing H3K27ac. Enhancers globally retaining mitotic H3K4me1 or locally retaining mitotic H3K27ac are associated with cell type-specific genes and their transcription factors for rapid transcriptional activation. As cells exit mitosis, promoters regain H3K27ac, which correlates with transcriptional reactivation. Insulators also gain H3K27ac and CCCTC-binding factor (CTCF) in anaphase/telophase. This increase of H3K27ac in anaphase/...

Circulation, Jan 29, 2017

Background -Bone Morphogenetic Protein (BMP) signaling has multiple roles in the development and ... more Background -Bone Morphogenetic Protein (BMP) signaling has multiple roles in the development and function of the blood vessels. In humans, mutations in BMP type 2 receptors (BMPR2), a key component of BMP signaling, have been identified in the majority of patients with familial pulmonary arterial hypertension (PAH). However, only a small subset of individuals with BMPR2 mutation develops PAH, suggesting that additional modifiers of BMPR2 function play an important role in the onset and progression of PAH. Methods -We utilized a combination of studies in zebrafish embryos and genetically engineered mice lacking endothelial expression of Vegfr3 to determine the interaction between VEGFR3 and BMPR2. Additional in vitro studies were performed using human endothelial cells, including primary endothelial cells from subjects with PAH. Results -Attenuation of Vegfr3 in zebrafish embryos abrogated Bmp2b-induced ectopic angiogenesis. Endothelial cells (ECs) with disrupted VEGFR3 expression fa...

Developmental Cell, 2012

Bone morphogenetic proteins (BMPs) have diverse functions during development in vertebrates. We h... more Bone morphogenetic proteins (BMPs) have diverse functions during development in vertebrates. We have recently shown that BMP2 signaling promotes venous-specific angiogenesis in zebrafish embryos. However, factors that confer a context-dependent proangiogenic function of BMP2 signaling within endothelial cells need to be identified. Here, we report that Disabled homolog 2 (Dab2), a cargospecific adaptor protein for Clathrin, is essential to mediate the proangiogenic function of BMP2 signaling. We find that inhibition of Dab2 attenuates internalization of BMP receptors and abrogates the proangiogenic effects of BMP signaling in endothelial cells. Moreover, inhibition of Dab2 decreases phosphorylation of SMAD-1, 5, and 8, indicating that Dab2 plays an essential role in determining the outcome of BMP signaling within endothelial cells and may provide a molecular basis for a contextdependent proangiogenic function of BMP2 signaling.

Arteriosclerosis, Thrombosis, and Vascular Biology, 2013

Objective— Apelin and its cognate receptor Aplnr/Apj are essential for diverse biological process... more Objective— Apelin and its cognate receptor Aplnr/Apj are essential for diverse biological processes. However, the function of Apelin signaling in lymphatic development remains to be identified, despite the preferential expression of Apelin and Aplnr within developing blood and lymphatic endothelial cells in vertebrates. In this report, we aim to delineate the functions of Apelin signaling during lymphatic development. Approach and Results— We investigated the functions of Apelin signaling during lymphatic development using zebrafish embryos and found that attenuation of Apelin signaling substantially decreased the formation of the parachordal vessel and the number of lymphatic endothelial cells within the developing thoracic duct, indicating an essential role of Apelin signaling during the early phase of lymphatic development. Mechanistically, we found that abrogation of Apelin signaling selectively attenuates lymphatic endothelial serine–threonine kinase Akt 1/2 phosphorylation wit...

Dynamic regulation of genome during cell division and at the nuclear periphery

In eukaryotes, the genome is hierarchically packaged inside the nucleus. The 3D organization of c... more In eukaryotes, the genome is hierarchically packaged inside the nucleus. The 3D organization of chromatin regulates various biological processes such as transcription, DNA replication, and cell division. The accurate gene regulation depends on when and where chromosomal interactions take place in the nucleus. This dissertation focuses on how the genome maintains its function after passing through mitosis and how the nuclear architecture at the nuclear periphery modulates transcription regulation.A long-standing question in the field is how cells maintain genome structure and function over multiple cell divisions, despite the loss of, for example, chromatin structure and gene expression during mitosis. In the first part of this dissertation, we determine that retention of histone modification binding contributes to accurate transcriptional programs and genome organization. We characterize the role of H3K27ac in the activation of post-mitotic transcription. An increase in H3K27ac bind...