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Heterochromatin rewiring and domain disruption-mediated chromatin compaction during erythropoiesis [RNA-seq]

ABSTRACT: Erythropoiesis in mammalian involves chromatin compaction which is initiated in the early stage of terminal differentiation. The proper condensation of chromatin is essential for the subsequent enucleation of erythroblast, but the characteristics of chromatin compaction and chromatin architecture changes in erythropoiesis are poorly understood. Here, we show that the formation of H3K9me3 long-range interactions which mediated heterochromatin three-dimensional rewiring participant in human erythroid chromatin condensation. TADs structure attenuated and boundary strength weakened globally but selectively maintaining in active chromatin region during terminal erythropoiesis. We demonstrate that the erythroid master regulators GATA1 safeguard the active chromatin structure and ensure the appropriate gene expression, under the chromatin condensation of human terminal erythropoiesis

ORGANISM(S): Homo sapiens

PROVIDER: GSE183992 | GEO | 2023/07/31

REPOSITORIES: GEO

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Heterochromatin rewiring and domain disruption-mediated chromatin compaction during erythropoiesis

Project description:Erythropoiesis in mammalian involves chromatin compaction which is initiated in the early stage of terminal differentiation. The proper condensation of chromatin is essential for the subsequent enucleation of erythroblast, but the characteristics of chromatin compaction and chromatin architecture changes in erythropoiesis are poorly understood. Here, we show that the formation of H3K9me3 long-range interactions which mediated heterochromatin three-dimensional rewiring participant in human erythroid chromatin condensation. TADs structure attenuated and boundary strength weakened globally but selectively maintaining in active chromatin region during terminal erythropoiesis. We demonstrate that the erythroid master regulators GATA1 safeguard the active chromatin structure and ensure the appropriate gene expression, under the chromatin condensation of human terminal erythropoiesis

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Heterochromatin rewiring and domain disruption-mediated chromatin compaction during erythropoiesis [HiChIP]

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Heterochromatin rewiring and domain disruption-mediated chromatin compaction during erythropoiesis [Mnase-seq]

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Heterochromatin rewiring and domain disruption-mediated chromatin compaction during erythropoiesis [CUT&RUN]

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Chromatin condensation is independent from nuclear condensation in late-stage terminal erythropoiesis revealed from the dynamic three-dimensional genomic organizations [Hi-C]

Project description:Mammalian terminal erythropoiesis involves chromatin and nuclear condensation followed by enucleation. Late-stage erythroblasts undergo caspase-mediated nuclear opening formation that is important for nuclear condensation through partial release of histones. It remains unknown whether nuclear opening and histone release influence the three-dimensional (3D) genomic organization during terminal erythropoiesis. Here, we compared the genome wide 3D organization, chromatin accessibility, and transcriptome of the cultured mouse erythroid progenitors with and without the blocking of nuclear opening during differentiation. We found that terminal differentiation from the basophilic to orthochromatic stages of erythroblasts involves compaction and establishment of long-range interactions of the heterochromatin regions, which is associated with globally increased accessibility and upregulation of erythroid-related genes. Surprisingly, blocking of nuclear opening did not have a significant impact on 3D genomic organization, chromatin accessibility, or transcriptome despite the inhibition of histone release and nuclear condensation. Inhibition of nuclear opening also significantly affected enucleation. We further demonstrated this through a caspase-3 and 7 double knockout mouse model, which showed significant defects in nuclear opening and condensation with a compromise of enucleation in fetal erythroid progenitors. However, loss of these effector caspases had minimal effects on the red cell indices and survival of the recipient animals in a fetal liver cell transplantation model. Overall, these results indicate that nuclear opening and histone release may not be necessary for chromatin condensation and global transcriptome but are critical for nuclear condensation and efficient enucleation. These data also underline the robustness of enucleation despite the dysplastic or less condensed nucleus.

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The three-dimensional genomic organization changes in terminal erythropoiesis reveal independence of chromatin condensation from nuclear condensation [RNA-Seq]

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The three-dimensional genomic organization changes in terminal erythropoiesis reveal independence of chromatin condensation from nuclear condensation [ATAC-Seq]

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Downregulation of Myc is essential for terminal erythroid maturation

Project description:Terminal differentiation of mammalian erythroid progenitors involves 4-5 cell divisions and induction of many erythroid important genes, followed by chromatin and nuclear condensation and enucleation. The protein levels of c-myc (Myc) are reduced dramatically during late stage erythroid maturation, coinciding with cell cycle arrest in G1-phase and enucleation, suggesting possible roles for c-myc in either or both of these processes. Here we demonstrate that ectopic Myc expression affects terminal erythroid maturation in a dose-dependent manner. Expression of Myc at physiological levels did not affect erythroid differentiation or cell cycle shutdown, but specifically blocked erythroid nuclear condensation and enucleation. Myc prevented deacetylation of several lysine residues in histones H3 and H4 that are normally deacetylated during erythroid maturation. When over-expressed at levels higher than the physiological range, Myc blocked erythroid differentiation and the cells continued to proliferate in cytokine-free, serum-containing culture medium with an early erythroblast morphology. These studies reveal an important dose-dependent function of Myc in regulating terminal maturation in mammalian erythroid cells. Our findings further support the emerging notion that Myc regulates chromatin structure by regulating global histone acetylation states. Five groups with three biological replicates in each.

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Histone H2A.X Phosphorylation Activates Caspase-Induced Chromatin Condensation in Late Stage Erythropoiesis

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