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- W4311880102 endingPage "143" @default.
- W4311880102 startingPage "117" @default.
- W4311880102 abstract "Abstract Nucleoli are nuclear compartments regulating ribosome biogenesis and cell growth. In embryonic stem cells (ESCs), nucleoli containing transcriptionally active ribosomal genes are spatially separated from pericentromeric satellite repeat sequences packaged in largely repressed constitutive heterochromatin (PCH). To date, mechanisms underlying such nuclear partitioning and the physiological relevance thereof are unknown. Here we show that repressive chromatin at PCH ensures structural integrity and function of nucleoli during cell cycle progression. Loss of heterochromatin proteins HP1α and HP1β causes deformation of PCH, with reduced H3K9 trimethylation (H3K9me3) and HP1γ levels, absence of H4K20me3 and upregulated major satellites expression. Spatially, derepressed PCH aberrantly associates with nucleoli accumulating severe morphological defects during S/G2 cell cycle progression. Hp1α/β deficiency reduces cell proliferation, ribosomal RNA biosynthesis and mobility of Nucleophosmin, a major nucleolar component. Nucleolar integrity and function require HP1α/β proteins to be recruited to H3K9me3-marked PCH and their ability to dimerize. Correspondingly, ESCs deficient for both Suv39h1/2 H3K9 HMTs display similar nucleolar defects. In contrast, Suv4-20h1/2 mutant ESCs lacking H4K20me3 at PCH do not. Suv39h1/2 and Hp1α/β deficiency-induced nucleolar defects are reminiscent of those defining human ribosomopathy disorders. Our results reveal a novel role for SUV39H/HP1-marked repressive constitutive heterochromatin in regulating integrity, function and physiology of nucleoli." @default.
- W4311880102 created "2023-01-02" @default.
- W4311880102 creator A5003229190 @default.
- W4311880102 creator A5007365367 @default.
- W4311880102 creator A5039723259 @default.
- W4311880102 creator A5057670341 @default.
- W4311880102 creator A5062052183 @default.
- W4311880102 creator A5069371064 @default.
- W4311880102 creator A5069745861 @default.
- W4311880102 creator A5079351788 @default.
- W4311880102 date "2022-12-19" @default.
- W4311880102 modified "2023-10-05" @default.
- W4311880102 title "HP1 proteins regulate nucleolar structure and function by secluding pericentromeric constitutive heterochromatin" @default.
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