Similar Datasets
Project description: Not available
| S-EPMC11869676 | biostudies-literature
Project description:Background: The three-dimensional chromatin niche provides a precise gene expression control of cell identity, differentiation, and disease development. CTCF is considered as the most essential transcription factor regulating chromatin architecture and gene expression. However, the genome-wide impact of CTCF on erythropoiesis has not yet been extensively investigated. Results: Here, using a state-of-the-art human erythroid progenitor cell model (HUDEP-2 and HEL cell lines), we systematically investigated the effects of acute CTCF loss by an auxin-inducible degron system on transcriptional programs, chromatin accessibility, CTCF genome occupancy, and the 3D genome architecture. By integrating multi-omics datasets, we revealed that acute CTCF loss notably disrupted genome-wide chromatin accessibility and transcription network. Importantly, we identified that over thousands of chromatin accessibility regions were decreased while only a few hundred increased regions after depletion of CTCF in both HUDEP-2 and HEL lines, suggesting the role of CTCF in maintaining the proper chromatin openness in erythroid lineage. Moreover, CTCF depletion in the erythroid context significantly disrupted TAD boundary integrity and chromatin loops while not affecting the nuclear compartmentalization. Our study also reported that hundreds of erythroid lineage-specific genes were suppressed in both immature and mature stages, including metabolism-related target genes such as GOT2 and FXN. Notably, we identified a subset of genes increased their transcriptional level after the CTCF depletion, accompanied by the decreased chromatin accessibility regions that were enriched with the GATA motif. Specifically, we identified that CTCF repressed the master transcription factor GATA2 with distal decreased chromatin regions via multiple functional studies, including CTCF occupancy profiling and CRISPR/Cas9 editing of the CTCF binding site. These results suggest a suppressive role of CTCF in gene expression in erythroid lineage specification. Conclusions: In summary, our results revealed a novel role of CTCF in regulating erythroid differentiation by maintaining its proper chromatin openness, which will undoubtedly extend our understanding of CTCF biology.
2025-01-27 | GSE282833 | GEO
Project description:Backgrounds：The three-dimensional chromatin niche provides a precise gene expression control of cell identity, differentiation, and disease development. CTCF is considered as the most essential transcription factor regulating chromatin architecture and gene expression. However, the genome-wide impact of CTCF on erythropoiesis has not yet been extensively investigated. Results：Here, using a state-of-the-art human erythroid progenitor cell model (HUDEP-2 and HEL cell lines), we systematically investigated the effects of acute CTCF loss by an auxin-inducible degron system on transcriptional programs, chromatin accessibility, CTCF genome occupancy, and the 3D genome architecture. By integrating multi-omics datasets, we revealed that acute CTCF loss notably disrupted genome-wide chromatin accessibility and transcription network. Importantly, we identified that over thousands of chromatin accessibility regions were decreased while only a few hundred increased regions after depletion of CTCF in both HUDEP-2 and HEL lines, suggesting the role of CTCF in maintaining the proper chromatin openness in erythroid lineage. Moreover, CTCF depletion in the erythroid context significantly disrupted TAD boundary integrity and chromatin loops while not affecting the nuclear compartmentalization. Our study also reported that hundreds of erythroid lineage-specific genes were suppressed in both immature and mature stages, including metabolism-related target genes such as GOT2 and FXN. Notably, we identified a subset of genes increased their transcriptional level after the CTCF depletion, accompanied by the decreased chromatin accessibility regions that were enriched with the GATA motif. Specifically, we identified that CTCF repressed the master transcription factor GATA2 with distal decreased chromatin regions via multiple functional studies, including CTCF occupancy profiling and CRISPR/Cas9 editing of the CTCF binding site. These results suggest a suppressive role of CTCF in gene expression in erythroid lineage specification. Conclusions：In summary, our results revealed a novel role of CTCF in regulating erythroid differentiation by maintaining its proper chromatin openness, which will undoubtedly extend our understanding of CTCF biology.
2025-01-27 | GSE282070 | GEO
Project description:The three-dimensional chromatin niche provides a precise gene expression control of cell identity, differentiation, and disease development. CTCF is considered as the master transcription factor regulating chromatin architecture and gene expression. However, the genome-wide impact of CTCF has not been extensively investigated due to the lack of proper research tools. Here, using a state-of-the-art auxin-inducible degron cellular model built up in human erythroid progenitors, we investigated the effects of acute CTCF loss on transcriptional programs and chromatin accessibility during human erythroid maturation. By integrating multi-omics datasets, we revealed that CTCF acute loss significantly disrupted genome-wide chromatin accessibility and transcription network. We further identified several direct novel target genes of CTCF in erythroid progenitor cells, including one master transcription factor GATA2 in hematopoiesis. Acute depletion of CTCF protein or disrupting CTCF binding sites in the topologically associated domains (TAD) boundary region of the GATA2 locus results in a significant transcriptional increase of GATA2. In summary, our results addressed a novel role of CTCF in regulating erythroid differentiation, which will undoubtedly extend our understanding of CTCF biology.
2025-01-27 | GSE201820 | GEO
Project description:The three-dimensional chromatin niche provides a precise gene expression control of cell identity, differentiation, and disease development. CTCF is considered as the master transcription factor regulating chromatin architecture and gene expression. However, the genome-wide impact of CTCF has not been extensively investigated due to the lack of proper research tools. Here, using a state-of-the-art auxin-inducible degron cellular model built up in human erythroid progenitors, we investigated the effects of acute CTCF loss on transcriptional programs and chromatin accessibility during human erythroid maturation. By integrating multi-omics datasets, we revealed that CTCF acute loss significantly disrupted genome-wide chromatin accessibility and transcription network. We further identified several direct novel target genes of CTCF in erythroid progenitor cells, including one master transcription factor GATA2 in hematopoiesis. Acute depletion of CTCF protein or disrupting CTCF binding sites in the topologically associated domains (TAD) boundary region of the GATA2 locus results in a significant transcriptional increase of GATA2. In summary, our results addressed a novel role of CTCF in regulating erythroid differentiation, which will undoubtedly extend our understanding of CTCF biology.
2025-01-27 | GSE201821 | GEO
Project description:The three-dimensional chromatin niche provides a precise gene expression control of cell identity, differentiation, and disease development. CTCF is considered as the most essential transcription factor regulating chromatin architecture and gene expression. However, the genome-wide impact of CTCF in erythropoiesis has not been extensively investigated yet. To further study the direct transcriptional regulatory role of CTCF, we established two endogenous C-terminus AID-CTCF system in t human erythroblast cell lines and systematically investigated the effects of acute CTCF loss by auxin-inducible degron system on transcriptional programs and chromatin accessibility. By integrating multi-omics datasets, we revealed that acute CTCF loss notably suppressed the subset of GATA1 downstream targets. Importantly, we revealed that acute CTCF loss notably disrupted genome-wide chromatin accessibility and transcription network. Importantly, we identified that over thousands of chromatin accessibility regions were decreased while only a few hundreds of increased regions after depletion of CTCF in both HUDEP-2 and HEL lines, suggesting the role of CTCF in maintaining the proper chromatin openness in erythroid lineage. Moreover, CTCF depletion in erythroid context significantly disrupted TAD boundary integrity and chromatin loops while not affecting the nuclear compartmentalization. In summary, our results addressed a novel role of CTCF in regulating erythroid differentiation by maintaining its proper chromatin openness, which will undoubtedly extend our understanding of CTCF biology.
2025-01-27 | GSE281733 | GEO
Project description:By using an unbiased genetic screen and proteome profiling in human erythroblast, we identified and verified KMT2D as an essential factor for human erythropoiesis. Accordingly, we observed that KMT2D is indispensable for the activation of erythroid signature genes in a stage dependent manner. Moreover, to further study the direct transcriptional regulatory role of KMT2D, we established two endogenous N-terminus AID-KMT2D system in t human erythroblast cell lines and systematically investigated the effects of acute KMT2D loss by auxin-inducible degron system on transcriptional programs and chromatin accessibility. By integrating multi-omics datasets, we revealed that acute KMT2D loss notably suppressed the subset of GATA1 downstream targets. Importantly, we profiled the specific genome-wide occupancy of KMT2D by comparison between the presence and absence of KMT2D in AID model. Strikingly, KMT2D occupies over hundreds of erythroid specific genes mostly on their promoters. More importantly, we revealed that the KMT2D co-localized with GATA1 in numerous erythroid genes and the occupancy of GATA1 significantly reduced after KMT2D degradation. These results suggest KMT2D is indispensable for the enhancer-binding of GATA1 in gene expression in erythroid lineage specification.
2025-01-27 | GSE281735 | GEO
Project description:The three-dimensional chromatin niche provides a precise gene expression control of cell identity, differentiation, and disease development. CTCF is considered as the most essential transcription factor regulating chromatin architecture and gene expression. However, the genome-wide impact of CTCF in erythropoiesis has not been extensively investigated yet. To further study the direct transcriptional regulatory role of CTCF, we established two endogenous C-terminus AID-CTCF system in t human erythroblast cell lines and systematically investigated the effects of acute CTCF loss by auxin-inducible degron system on transcriptional programs and chromatin accessibility. By integrating multi-omics datasets, we revealed that acute CTCF loss notably suppressed the subset of GATA1 downstream targets. Importantly, we revealed that acute CTCF loss notably disrupted genome-wide chromatin accessibility and transcription network. Importantly, we identified that over thousands of chromatin accessibility regions were decreased while only a few hundreds of increased regions after depletion of CTCF in both HUDEP-2 and HEL lines, suggesting the role of CTCF in maintaining the proper chromatin openness in erythroid lineage. Moreover, CTCF depletion in erythroid context significantly disrupted TAD boundary integrity and chromatin loops while not affecting the nuclear compartmentalization. In summary, our results addressed a novel role of CTCF in regulating erythroid differentiation by maintaining its proper chromatin openness, which will undoubtedly extend our understanding of CTCF biology.
2025-01-27 | GSE281734 | GEO
Project description:CTCF is selectively required for maintaining chromatin accessibility and gene expression in human erythropoiesis
| PRJNA1186944 | ENA
Project description:CTCF is selectively required for maintaining chromatin accessibility and gene expression in human erythropoiesis
| PRJNA1190492 | ENA