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

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE185470 | GEO | 2022/12/16

REPOSITORIES: GEO

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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.

2022-12-16 | GSE185469 | GEO

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

2022-12-16 | GSE185468 | GEO

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

Project description:The three-dimensional genomic organization changes in terminal erythropoiesis reveal independence of chromatin condensation from nuclear condensation

| PRJNA769134 | ENA

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

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

| PRJNA769217 | ENA

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

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

| PRJNA769216 | ENA

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

2022-12-16 | GSE184974 | GEO

Three-dimensional Nuclear Telomere Organization in Multiple Myeloma.

Project description:Multiple myeloma (MM) is preceded by monoclonal gammopathy of undetermined significance (MGUS). Up to date, it is difficult to predict an individual's time to disease progression and the treatment response. To examine whether the nuclear telomeric architecture will unravel some of these questions, we carried out. Three-dimensional (3D) telomere analysis on samples from patients diagnosed with MGUS and MM, as well as from patients who went into relapse. Telomere signal intensity, number of telomere aggregates, nuclear volume, and the overall nuclear telomere distribution (a/c ratio) were analyzed. The telomeric profiles allowed for the differentiation of the disease stages. The telomeric profiles of myeloma cells obtained from blood and bone marrow aspirates were identical. Based on this study, we discuss the use of 3D telomere profiling as a potential future tool for risk stratification and personalized treatment decisions.

| S-EPMC3890710 | biostudies-literature

Nuclear Condensation during Mouse Erythropoiesis Requires Caspase-3-Mediated Nuclear Opening.

Project description:Mammalian erythropoiesis involves chromatin condensation that is initiated in the early stage of terminal differentiation. The mechanisms of chromatin condensation during erythropoiesis are unclear. Here, we show that the mouse erythroblast forms large, transient, and recurrent nuclear openings that coincide with the condensation process. The opening lacks nuclear lamina, nuclear pore complexes, and nuclear membrane, but it is distinct from nuclear envelope changes that occur during apoptosis and mitosis. A fraction of the major histones are released from the nuclear opening and degraded in the cytoplasm. We demonstrate that caspase-3 is required for the nuclear opening formation throughout terminal erythropoiesis. Loss of caspase-3 or ectopic expression of a caspase-3 non-cleavable lamin B mutant blocks nuclear opening formation, histone release, chromatin condensation, and terminal erythroid differentiation. We conclude that caspase-3-mediated nuclear opening formation accompanied by histone release from the opening is a critical step toward chromatin condensation during erythropoiesis in mice.

| S-EPMC4785602 | biostudies-literature

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

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

| PRJNA767263 | ENA

Glucocorticoid receptor and nuclear factor kappa-b affect three-dimensional chromatin organization.

Project description:BackgroundThe impact of signal-dependent transcription factors, such as glucocorticoid receptor and nuclear factor kappa-b, on the three-dimensional organization of chromatin remains a topic of discussion. The possible scenarios range from remodeling of higher order chromatin architecture by activated transcription factors to recruitment of activated transcription factors to pre-established long-range interactions.ResultsUsing circular chromosome conformation capture coupled with next generation sequencing and high-resolution chromatin interaction analysis by paired-end tag sequencing of P300, we observed agonist-induced changes in long-range chromatin interactions, and uncovered interconnected enhancer-enhancer hubs spanning up to one megabase. The vast majority of activated glucocorticoid receptor and nuclear factor kappa-b appeared to join pre-existing P300 enhancer hubs without affecting the chromatin conformation. In contrast, binding of the activated transcription factors to loci with their consensus response elements led to the increased formation of an active epigenetic state of enhancers and a significant increase in long-range interactions within pre-existing enhancer networks. De novo enhancers or ligand-responsive enhancer hubs preferentially interacted with ligand-induced genes.ConclusionsWe demonstrate that, at a subset of genomic loci, ligand-mediated induction leads to active enhancer formation and an increase in long-range interactions, facilitating efficient regulation of target genes. Therefore, our data suggest an active role of signal-dependent transcription factors in chromatin and long-range interaction remodeling.

| S-EPMC4665721 | biostudies-literature

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