CTCF overexpression in K562
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE319471 | GEO | 2026/04/27
REPOSITORIES: GEO
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Project description:Gene expression during cellular differentiation is coordinated by combinatorial interactions between transcription factors (TFs) and cofactors at promoters and enhancers. The “master TF” GATA1 coordinates gene transcription in a subset of hematopoietic lineages, including erythroid, megakaryocytic, mast, and eosinophil, while repressing the development of other blood lineages. However, the specific cofactors required for GATA1-activated gene expression during hematopoiesis are incompletely defined. We identified the cofactor KMT2D, an H3K4 methyltransferase that collaborates with H3K27 acetyltransferases to activate transcription, in an unbiased CRISPR/Cas9 screen for epigenetic regulators of erythropoiesis. Loss of KMT2D in human erythroid precursors caused developmental arrest with impaired expression of numerous erythroid genes. Mechanistically, KMT2D colocalized with GATA1 on more than one thousand erythroid enhancers associated with over two hundred erythroid genes. In general, co-occupancy of GATA1 and KMT2D at erythroid enhancers was associated with stronger transcriptional activity than occupancy by GATA1 alone. Acute depletion of KMT2D in erythroid precursors caused rapid reductions of H3K4me1 and H3K27ac on a subset of GATA1-bound enhancers and impaired the expression of canonical erythroid genes, including ZFPM1, SLC4A1, and EPOR. Moreover, acute depletion of GATA1 or KMT2D individually caused downregulation of overlapping gene sets. Thus, KMT2D controls erythropoiesis by selectively activating GATA1-dependent erythroid enhancers. Our studies identify KMT2D as a novel cofactor for transcriptional activation by GATA1 during erythropoiesis. More generally, our findings demonstrate how a lineage-specific TF cooperates with a ubiquitous epigenetic regulator to drive lineage-specific gene expression during cellular differentiation.
2026-04-10 | PXD076443 | Pride
Project description:Gene expression during cellular differentiation is coordinated by combinatorial interactions between transcription factors (TFs) and cofactors at promoters and enhancers. The “master TF” GATA1 coordinates gene transcription in a subset of hematopoietic lineages, including erythroid, megakaryocytic, mast, and eosinophil, while repressing the development of other blood lineages. However, the specific cofactors required for GATA1-activated gene expression during hematopoiesis are incompletely defined. We identified the cofactor KMT2D, an H3K4 methyltransferase that collaborates with H3K27 acetyltransferases to activate transcription, in an unbiased CRISPR/Cas9 screen for epigenetic regulators of erythropoiesis. Loss of KMT2D in human erythroid precursors caused developmental arrest with impaired expression of numerous erythroid genes. Mechanistically, KMT2D colocalized with GATA1 on more than one thousand erythroid enhancers associated with over two hundred erythroid genes. In general, co-occupancy of GATA1 and KMT2D at erythroid enhancers was associated with stronger transcriptional activity than occupancy by GATA1 alone. Acute depletion of KMT2D in erythroid precursors caused rapid reductions of H3K4me1 and H3K27ac on a subset of GATA1-bound enhancers and impaired the expression of canonical erythroid genes, including ZFPM1, SLC4A1, and EPOR. Moreover, acute depletion of GATA1 or KMT2D individually caused downregulation of overlapping gene sets. Thus, KMT2D controls erythropoiesis by selectively activating GATA1-dependent erythroid enhancers. Our studies identify KMT2D as a novel cofactor for transcriptional activation by GATA1 during erythropoiesis. More generally, our findings demonstrate how a lineage-specific TF cooperates with a ubiquitous epigenetic regulator to drive lineage-specific gene expression during cellular differentiation.
2026-04-10 | GSE319078 | GEO
Project description:Gene expression during cellular differentiation is coordinated by combinatorial interactions between transcription factors (TFs) and cofactors at promoters and enhancers. The “master TF” GATA1 coordinates gene transcription in a subset of hematopoietic lineages, including erythroid, megakaryocytic, mast, and eosinophil, while repressing the development of other blood lineages. However, the specific cofactors required for GATA1-activated gene expression during hematopoiesis are incompletely defined. We identified the cofactor KMT2D, an H3K4 methyltransferase that collaborates with H3K27 acetyltransferases to activate transcription, in an unbiased CRISPR/Cas9 screen for epigenetic regulators of erythropoiesis. Loss of KMT2D in human erythroid precursors caused developmental arrest with impaired expression of numerous erythroid genes. Mechanistically, KMT2D colocalized with GATA1 on more than one thousand erythroid enhancers associated with over two hundred erythroid genes. In general, co-occupancy of GATA1 and KMT2D at erythroid enhancers was associated with stronger transcriptional activity than occupancy by GATA1 alone. Acute depletion of KMT2D in erythroid precursors caused rapid reductions of H3K4me1 and H3K27ac on a subset of GATA1-bound enhancers and impaired the expression of canonical erythroid genes, including ZFPM1, SLC4A1, and EPOR. Moreover, acute depletion of GATA1 or KMT2D individually caused downregulation of overlapping gene sets. Thus, KMT2D controls erythropoiesis by selectively activating GATA1-dependent erythroid enhancers. Our studies identify KMT2D as a novel cofactor for transcriptional activation by GATA1 during erythropoiesis. More generally, our findings demonstrate how a lineage-specific TF cooperates with a ubiquitous epigenetic regulator to drive lineage-specific gene expression during cellular differentiation.
2026-04-10 | GSE319076 | GEO
Project description:Gene expression during cellular differentiation is coordinated by combinatorial interactions between transcription factors (TFs) and cofactors at promoters and enhancers. The “master TF” GATA1 coordinates gene transcription in a subset of hematopoietic lineages, including erythroid, megakaryocytic, mast, and eosinophil, while repressing the development of other blood lineages. However, the specific cofactors required for GATA1-activated gene expression during hematopoiesis are incompletely defined. We identified the cofactor KMT2D, an H3K4 methyltransferase that collaborates with H3K27 acetyltransferases to activate transcription, in an unbiased CRISPR/Cas9 screen for epigenetic regulators of erythropoiesis. Loss of KMT2D in human erythroid precursors caused developmental arrest with impaired expression of numerous erythroid genes. Mechanistically, KMT2D colocalized with GATA1 on more than one thousand erythroid enhancers associated with over two hundred erythroid genes. In general, co-occupancy of GATA1 and KMT2D at erythroid enhancers was associated with stronger transcriptional activity than occupancy by GATA1 alone. Acute depletion of KMT2D in erythroid precursors caused rapid reductions of H3K4me1 and H3K27ac on a subset of GATA1-bound enhancers and impaired the expression of canonical erythroid genes, including ZFPM1, SLC4A1, and EPOR. Moreover, acute depletion of GATA1 or KMT2D individually caused downregulation of overlapping gene sets. Thus, KMT2D controls erythropoiesis by selectively activating GATA1-dependent erythroid enhancers. Our studies identify KMT2D as a novel cofactor for transcriptional activation by GATA1 during erythropoiesis. More generally, our findings demonstrate how a lineage-specific TF cooperates with a ubiquitous epigenetic regulator to drive lineage-specific gene expression during cellular differentiation.
2026-04-10 | GSE319075 | GEO
Project description:Gene expression during cellular differentiation is coordinated by combinatorial interactions between transcription factors (TFs) and cofactors at promoters and enhancers. The “master TF” GATA1 coordinates gene transcription in a subset of hematopoietic lineages, including erythroid, megakaryocytic, mast and eosinophil, while repressing the development of other blood lineages. However, the specific cofactors required for GATA1-activated gene expression during hematopoiesis are incompletely defined. We identified the cofactor KMT2D in an unbiased CRISPR/Cas9 screen for epigenetic regulators of erythropoiesis. Loss of KMT2D in human erythroid precursors caused developmental arrest with impaired expression of numerous erythroid genes. Mechanistically, KMT2D belongs to a family of H3K4 methyltransferases that collaborate with H3K27 acetyltransferases to activate transcription. KMT2D colocalized with GATA1 on more than one thousand erythroid enhancers associated with over two hundreds erythroid genes. In general, co-occupancy of GATA1 and KMT2D at erythroid enhancers was associated with stronger transcriptional activity than occupancy by GATA1 alone. Acute depletion of KMT2D in erythroid precursors caused rapid reductions of H3K4me1 and H3K27ac on a subset of GATA1-bound enhancers and impaired the expression of canonical erythroid genes including ZFPM1, SLC4A1, and EPOR. Moreover, acute depletion of GATA1 or KMT2D individually caused downregulation of overlapping genes. Thus, KMT2D controls erythropoiesis by selectively activating GATA1-dependent erythroid enhancers. Our studies identify KMT2D as a novel cofactor for transcriptional activation by GATA1 during erythropoiesis. More generally, our findings demonstrate how a lineage-specific TF cooperates with a ubiquitous epigenic regulator to drive lineage-specific gene expression during cellular differentiation.
2026-04-10 | GSE275664 | GEO
Project description:Preeclampsia (PE) has been associated with placental dysfunction, resulting in foetal hypoxia, accelerated erythropoiesis and increased erythroblast count in the umbilical cord blood (UCB). Although the detailed effects remain unknown, placental dysfunction can also cause inflammation, nutritional and oxidative stress in the fetus that can affect erythropoiesis. Here, we compared the expression of surface adhesion molecules and erythroid differentiation capacity of UCB hematopoietic stem/ progenitor cells (HSPCs), UCB erythroid profiles along with transcriptome and proteome of these cells between male and female foetuses from PE and normotensive pregnancies. While no significant differences were observed in UCB HSPC migration/ homing and in vitro erythroid colony differentiation, the UCB HSPC transcriptome and the proteomic profile of the in vitro differentiated erythroid cells differed between PE vs normotensive samples. Accordingly, despite absence of significant differences in the UCB erythroid populations in male or female foetuses from PE or normotensive pregnancies, transcriptional changes were observed during erythropoiesis, particularly affecting male foetuses. Pathway analysis suggested deregulation in mTORC1/AMPK signaling pathways controlling cell cycle, differentiation and protein synthesis. These results associate PE with transcriptional and proteomic changes in foetal HSPCs and erythroid cells that may underlie the higher erythroblast count in the UCB in PE.
2019-06-20 | PXD010364 | Pride
Project description:Human erythropoiesis is a stepwise process in which multipotent hematopoietic stem/progenitor cells (HSPC) are initially committed towards the erythroid lineage and then differentiated into mature erythroid precursors. Commitment and differentiation are tightly regulated by the coordinated action of a host of transcription factors, including GATA2 and GATA1. Although the role of GATA factors in erythropoiesis has been extensively studied, how they regulate transcription from early to late stages of human erythropoiesis still remains underinvestigated. Here, we investigated GATA-mediated transcriptional regulation along erythroid development through the integrative analysis of gene expression, chromatin modifications, and GATA factors’ binding in human HSPC, early erythroid progenitors, and late precursors. A progressive loss of H3K27 acetylation, a mark of active regulatory elements, and diminished usage of active enhancers and super-enhancers was observed during erythroid lineage commitment and differentiation. We found that GATA factors mediate the transcriptional changes occurring during erythropoiesis through a stage-specific interplay with regulatory elements. In particular, GATA1 binds different sets of regulatory elements in early progenitors and late precursors, and controls the transcription of distinct genes in commitment and differentiation. By Chromosome Conformation Capture and CRISPR/Cas9-mediated genome editing, we demonstrated that the binding of GATA1 to a stage-specific super-enhancer sustains the expression of the stem cell factor receptor KIT in human erythroid progenitors. This study provides insights into the dynamics of epigenetic and transcriptional interactions during erythroid development and highlights a new layer of GATA1-mediated regulation in erythropoiesis.
2020-04-10 | GSE124164 | GEO
Project description:Human erythropoiesis is a stepwise process in which multipotent hematopoietic stem/progenitor cells (HSPC) are initially committed towards the erythroid lineage and then differentiated into mature erythroid precursors. Commitment and differentiation are tightly regulated by the coordinated action of a host of transcription factors, including GATA2 and GATA1. Although the role of GATA factors in erythropoiesis has been extensively studied, how they regulate transcription from early to late stages of human erythropoiesis still remains underinvestigated. Here, we investigated GATA-mediated transcriptional regulation along erythroid development through the integrative analysis of gene expression, chromatin modifications, and GATA factors’ binding in human HSPC, early erythroid progenitors, and late precursors. A progressive loss of H3K27 acetylation, a mark of active regulatory elements, and diminished usage of active enhancers and super-enhancers was observed during erythroid lineage commitment and differentiation. We found that GATA factors mediate the transcriptional changes occurring during erythropoiesis through a stage-specific interplay with regulatory elements. In particular, GATA1 binds different sets of regulatory elements in early progenitors and late precursors, and controls the transcription of distinct genes in commitment and differentiation. By Chromosome Conformation Capture and CRISPR/Cas9-mediated genome editing, we demonstrated that the binding of GATA1 to a stage-specific super-enhancer sustains the expression of the stem cell factor receptor KIT in human erythroid progenitors. This study provides insights into the dynamics of epigenetic and transcriptional interactions during erythroid development and highlights a new layer of GATA1-mediated regulation in erythropoiesis.
2020-04-10 | GSE124163 | GEO
Project description:We performed a proteomic analysis of human erythropoiesis using 4 umbilical cord's blood samples. This study revealed the absolute and quantitative expression of more than 6000 proteins throughout 7 stages of erythroid differentiation using a label-free technique. We found new informations on erythropoiesis such as unexpected protein expression depicted the article.
2016-08-08 | PXD004313 | Pride
Project description:We performed a proteomic analysis of human erythropoiesis using 4 umbilical cord's blood samples. This study revealed the absolute and quantitative expression of more than 6000 proteins throughout 7 stages of erythroid differentiation using a label-free technique. We found new informations on erythropoiesis such as unexpected protein expression depicted the article.
2016-08-08 | PXD004314 | Pride