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

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: GSE183989 | 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 [RNA-seq]

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

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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