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| Status |
Public on Sep 09, 2020 |
| Title |
H1 linker histones regulate the balance of repressive and active chromatin domains via localized genomic compaction [ATAC-seq] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
H1 linker histones are the most abundant chromatin binding proteins. Their association with chromatin determines the spacing between nucleosomes and enables arrays of nucleosomes to fold into more compact chromatin structures. Mammals express multiple H1 proteins and are able to compensate for the loss of one or even two members by increasing synthesis of other members to maintain a constant H1 to nucleosome stoichiometry. To study the role of H1 in mammalian development, we generated a conditional triple H1 knockout (H1cTKO) mouse strain that enables depletion of H1 in specific cell types. Here, we report on the effects of depleting H1 in adult hematopoietic cells. Deletion of the genes encoding three widely expressed H1 subtypes (H1c, H1d, and H1e) has particularly profound effects on B- and T- lymphocyte development. H1 depletion leads to de-repression of T-cell activation genes, and a shift in T-cells towards effector functions, a process that mimics normal T-cell activation. Comparison of chromatin structure in normal and H1-depleted CD8+ T-cells revealed that H1 binding produces localized chromatin compaction within spatially defined chromatin domains containing above average levels of H1. Reduction of H1 stoichiometry in these regions leads to decreases in H3K27 methylation and increases in H3K36 methylation. In vitro, H1 promotes PRC2-mediated H3K27 methylation and inhibits NSD2-mediated H3K36 methylation. Mechanistically, H1 mediates these opposite effects by promoting physical compaction of the chromatin substrate. These findings identify H1 as a critical regulator of the epigenetic landscape in mammalian cells.
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| Overall design |
CD4+ or CD8+ splenic T cells, as well as peripheral blood B cells were isolated from adult C57BL/6 WT or H1 cTKO mice, with 2 independent replicates for most samples and 4 for CD4+ T cells.
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| Contributor(s) |
Healton SE, Weiss CN, Bartholdy B, Willcockson MA, Skoultchi AI |
| Citation(s) |
33299182 |
| |
| Submission date |
Nov 29, 2019 |
| Last update date |
Dec 10, 2020 |
| Contact name |
Boris Bartholdy |
| Organization name |
Albert Einstein College of Medicine
|
| Department |
Cell Biology
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| Street address |
1300 Morris Park Ave
|
| City |
Bronx |
| State/province |
NY |
| ZIP/Postal code |
10461 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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| Samples (16)
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| This SubSeries is part of SuperSeries: |
| GSE141187 |
H1 linker histones regulate the balance of repressive and active chromatin domains via localized genomic compaction |
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| Relations |
| BioProject |
PRJNA592605 |
| SRA |
SRP235118 |
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