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RNA-seq profiles of DP thymocytes from control and Suv39h1/Suv39h2 double knockout mice

ABSTRACT: H3K9me3-dependent heterochromatin is critical for the silencing of repeat-rich pericentromeric regions and also has key roles in repressing lineage-inappropriate protein-coding genes for healthy cellular function. Here we investigate the transcriptomic effects of heterochromatin loss in primary immune cells deficient in both Suv39h1 and Suv39h2 (Suv39DKO), the major mammalian histone methyltransferase enzymes which catalyse heterochromatic H3K9me3 deposition.

ORGANISM(S): Mus musculus

PROVIDER: GSE156296 | GEO | 2024/03/27

REPOSITORIES: GEO

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ATAC-seq of DP thymocytes from Suv39h1 and Suv39h2 double knockout chimeric mice

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Project description:Recent studies have shown that repressive chromatin machinery, including DNA methyltransferases and Polycomb Repressor Complexes, bind to chromosomes throughout mitosis and their depletion results in increased chromosome size. Here we show that enzymes that catalyse H3K9 methylation, such as Suv39h1, Suv39h2, G9a and Glp, are also retained on mitotic chromosomes. Surprisingly however, mutants lacking H3K9me3 have unusually small and compact mitotic chromosomes associated with increased H3S10ph and H3K27me3 levels. Chromosome size and centromere compaction in these mutants were rescued by providing exogenous Suv39h1, or inhibiting Ezh2 activity. Quantitative proteomic comparisons of native mitotic chromosomes isolated from wildtype versus Suv39h1/Suv39h2 double-null mouse ESCs revealed that H3K9me3 was essential for the efficient retention of bookmarking factors such as Esrrb. These results highlight an unexpected role for repressive heterochromatin domains in preserving transcription factor binding through mitosis, and underscore the importance of H3K9me3 for sustaining chromosome architecture and epigenetic memory during cell division.

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Project description:ATAC-seq of DP thymocytes from Suv39h1 and Suv39h2 double knockout chimeric mice

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Loss of H3K9 tri-methylation alters mitotic chromosome compaction and transcription factor retention during mitosis

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RNA-seq profiles of DP thymocytes from control and Suv39h1/Suv39h2 double knockout mice

Project description:RNA-seq profiles of DP thymocytes from control and Suv39h1/Suv39h2 double knockout mice

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