RNA-dependent stabilization of SUV39H1 at constitutive heterochromatin.

Abstract:

: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 α-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 α-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.

journal_name

Elife

journal_title

eLife

authors

Johnson WL,Yewdell WT,Bell JC,McNulty SM,Duda Z,O'Neill RJ,Sullivan BA,Straight AF

doi

10.7554/eLife.25299

subject

Has Abstract

pub_date

2017-08-01 00:00:00

issn

2050-084X

journal_volume

6

pub_type

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