Genome accessibility is widely preserved and locally modulated during mitosis

  1. Gerd A. Blobel1
  1. 1Division of Hematology, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA;
  2. 2Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA;
  3. 3Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, Pennsylvania 16802, USA;
  4. 4Institute for Genome Sciences and Policy, Duke University, Durham, North Carolina 27708, USA;
  5. 5Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA;
  6. 6Center for Genomic and Computational Biology, Duke University, Durham, North Carolina 27708, USA;
  7. 7Department of Pediatrics, Division of Medical Genetics, Duke University, Durham, North Carolina 27708, USA
  1. Corresponding author: blobel{at}email.chop.edu

  1. ↵8 These authors contributed equally to this work.

Abstract

Mitosis entails global alterations to chromosome structure and nuclear architecture, concomitant with transient silencing of transcription. How cells transmit transcriptional states through mitosis remains incompletely understood. While many nuclear factors dissociate from mitotic chromosomes, the observation that certain nuclear factors and chromatin features remain associated with individual loci during mitosis originated the hypothesis that such mitotically retained molecular signatures could provide transcriptional memory through mitosis. To understand the role of chromatin structure in mitotic memory, we performed the first genome-wide comparison of DNase I sensitivity of chromatin in mitosis and interphase, using a murine erythroblast model. Despite chromosome condensation during mitosis visible by microscopy, the landscape of chromatin accessibility at the macromolecular level is largely unaltered. However, mitotic chromatin accessibility is locally dynamic, with individual loci maintaining none, some, or all of their interphase accessibility. Mitotic reduction in accessibility occurs primarily within narrow, highly DNase hypersensitive sites that frequently coincide with transcription factor binding sites, whereas broader domains of moderate accessibility tend to be more stable. In mitosis, proximal promoters generally maintain their accessibility more strongly, whereas distal regulatory elements tend to lose accessibility. Large domains of DNA hypomethylation mark a subset of promoters that retain accessibility during mitosis and across many cell types in interphase. Erythroid transcription factor GATA1 exerts site-specific changes in interphase accessibility that are most pronounced at distal regulatory elements, but has little influence on mitotic accessibility. We conclude that features of open chromatin are remarkably stable through mitosis, but are modulated at the level of individual genes and regulatory elements.

Footnotes

  • Received June 28, 2014.
  • Accepted November 3, 2014.

This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.

| Table of Contents

This Article

  1. Published in Advance November 4, 2014, doi: 10.1101/gr.180646.114 Genome Res. 25: 213-225 © 2015 Hsiung et al.; Published by Cold Spring Harbor Laboratory Press

Article Category

Share

Preprint Server



Current Issue

  1. March 2024, 34 (3)
  1. Current Issue
  1. Alert me to new issues of Genome Research