Journal
ELIFE
Volume 6, Issue -, Pages -Publisher
ELIFE SCIENCES PUBLICATIONS LTD
DOI: 10.7554/eLife.25299
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Funding
- National Institutes of Health [GM007276, GM116378, GM098500]
- National Science Foundation [DGE-114747, DGE-1644868, 121132]
- Stanford University School of Medicine Stanford Graduate Fellowship Program
- Stanford University School of Medicine Dean's Postdoctoral Fellowship
- March of Dimes Foundation [1-FY13-517]
- American Cancer Society [12061-RSG-11-025-01-CCG]
- Div Of Molecular and Cellular Bioscience
- Direct For Biological Sciences [1613806] Funding Source: National Science Foundation
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Heterochromatin formed by the SUV39 histone methyltransferases represses transcription from repetitive DNA sequences and ensures genomic stability. How SUV39 enzymes localize to their target genomic loci remains unclear. Here, we demonstrate that chromatin-associated RNA contributes to the stable association of SUV39H1 with constitutive heterochromatin in human cells. We find that RNA associated with mitotic chromosomes is concentrated at pericentric heterochromatin, and is encoded, in part, by repetitive alpha-satellite sequences, which are retained in cis at their transcription sites. Purified SUV39H1 directly binds nucleic acids through its chromodomain; and in cells, SUV39H1 associates with alpha-satellite RNA transcripts. Furthermore, nucleic acid binding mutants destabilize the association of SUV39H1 with chromatin in mitotic and interphase cells - effects that can be recapitulated by RNase treatment or RNA polymerase inhibition - and cause defects in heterochromatin function. Collectively, our findings uncover a previously unrealized function for chromatin-associated RNA in regulating constitutive heterochromatin in human cells.
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