RNA-dependent stabilization of SUV39H1 at constitutive heterochromatin

Loading...
Thumbnail Image

Date

2017-08-01

Journal Title

Journal ISSN

Volume Title

Repository Usage Stats

45
views
17
downloads

Citation Stats

Abstract

© Johnson et al. 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 a-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 a-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.

Department

Description

Provenance

Subjects

Citation

Published Version (Please cite this version)

10.7554/eLife.25299.001

Publication Info

Johnson, WL, WT Yewdell, JC Bell, SM McNulty, Z Duda, RJ O’Neill, BA Sullivan, AF Straight, et al. (2017). RNA-dependent stabilization of SUV39H1 at constitutive heterochromatin. eLife, 6. 10.7554/eLife.25299.001 Retrieved from https://hdl.handle.net/10161/21536.

This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.

Scholars@Duke

Sullivan

Beth Ann Sullivan

James B. Duke Distinguished Professor

Research in the Sullivan Lab is focused on chromosome organization, with a specific emphasis on the genomics and epigenetics of the chromosomal locus called the centromere. The centromere is a specialized chromosomal site involved in chromosome architecture and movement, and when defective, is linked to cancer, birth defects, and infertility. The lab has described a unique type of chromatin (CEN chromatin) that forms exclusively at the centromere by replacement of core histone H3 by the centromeric histone variant CENP-A. Their studies also explore the composition of CEN chromatin and its relationship to the underlying highly repetitive alpha satellite DNA at the centromere. The Sullivan lab also discovered that genomic variation within alpha satellite DNA affects where the centromere is built and how well it functions. The Sullivan lab was part of the Telomere-to-Telomere T2T Consortium that used ultra long read sequencing and optical mapping to completely assemble each human chromosome, including through millions of basepairs of alpha satellite DNA at each centromere. Dr. Sullivan's group also builds human artificial chromosomes (HACs), using them as tools to test components required for a viable, transmissible chromosome and to study centromeric transcription and chromosome stability. The lab also studies formation and fate of chromosome abnormalities associated with birth defects, reproductive abnormalities, and cancer. Specifically, they study chromosomal abnormalities with two centromeres, called dicentric chromosomes. Originally described by Nobelist Barbara McClintock in the 1930s, dicentrics in most organisms are considered inherently unstable chromosomes because they trigger genome instability. However, dicentric chromosomes in humans are very stable and are often transmitted through multiple generations of a family. Using several approaches to experimentally reproduce dicentric chromosomes in human cells, the lab explores mechanisms of dicentric formation and their long-term fate.


Unless otherwise indicated, scholarly articles published by Duke faculty members are made available here with a CC-BY-NC (Creative Commons Attribution Non-Commercial) license, as enabled by the Duke Open Access Policy. If you wish to use the materials in ways not already permitted under CC-BY-NC, please consult the copyright owner. Other materials are made available here through the author’s grant of a non-exclusive license to make their work openly accessible.