RNA-dependent stabilization of SUV39H1 at constitutive heterochromatin.

Published online

Journal Article

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.

Full Text

Duke Authors

Cited Authors

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

Published Date

  • August 1, 2017

Published In

Volume / Issue

  • 6 /

PubMed ID

  • 28760200

Pubmed Central ID

  • 28760200

Electronic International Standard Serial Number (EISSN)

  • 2050-084X

Digital Object Identifier (DOI)

  • 10.7554/eLife.25299

Language

  • eng

Conference Location

  • England