Binding of an X-specific condensin correlates with a reduction in active histone modifications at gene regulatory elements

Lena Annika Street, Ana Karina Morao, Lara Heermans Winterkorn, Chen Yu Jiao, Sarah Elizabeth Albritton, Mohammed Sadic, Maxwell Kramer, Sevinç Ercan

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Condensins are evolutionarily conserved protein complexes that are required for chromosome segregation during cell division and genome organization during interphase. In Caenorhabditis elegans, a specialized condensin, which forms the core of the dosage compensation complex (DCC), binds to and represses X chromosome transcription. Here, we analyzed DCC localization and the effect of DCC depletion on histone modifications, transcription factor binding, and gene expression using chromatin immunoprecipitation sequencing and mRNA sequencing. Across the X, the DCC accumulates at accessible gene regulatory sites in active chromatin and not heterochromatin. The DCC is required for reducing the levels of activating histone modifications, including H3K4me3 and H3K27ac, but not repressive modification H3K9me3. In X-to-autosome fusion chromosomes, DCC spreading into the autosomal sequences locally reduces gene expression, thus establishing a direct link between DCC binding and repression. Together, our results indicate that DCC-mediated transcription repression is associated with a reduction in the activity of X chromosomal gene regulatory elements.

Original languageEnglish (US)
Pages (from-to)729-742
Number of pages14
JournalGenetics
Volume212
Issue number3
DOIs
StatePublished - Jul 2019
Externally publishedYes

Bibliographical note

Funding Information:
We thank Susan Gasser for providing the GW638 strain; Dominic Balcon and Jacob Carmichael for help with growing worms; the New York University (NYU) Center for Genomics and Systems Biology, University of North Carolina, and the Max Delbr?ck Center for Molecular Medicine, Berlin highthroughput sequencing facilities for sequencing; and Gyorgyi Csankovszki for providing the H4K16 antibody. Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institutes of Health (NIH) under grant number R01 GM-107293. Some strains were provided by the Caenorhabditis Genetics Center, which is funded by the NIH Office of Research Infrastructure Programs (P40 OD-010440). The mass spectrometry was funded in part by an NYU School of Medicine Laura and Isaac Perlmutter Cancer Center grant from the National Cancer Institute (P30 CA-016087), and a shared instrumentation grant for an Orbitrap Fusion Lumos (1S10 OD-010582- 01A1).

Funding Information:
We thank Susan Gasser for providing the GW638 strain; Dominic Balcon and Jacob Carmichael for help with growing worms; the New York University (NYU) Center for Genomics and Systems Biology, University of North Carolina, and the Max Delbrück Center for Molecular Medicine, Berlin high-throughput sequencing facilities for sequencing; and Gyorgyi Csankovszki for providing the H4K16 antibody. Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institutes of Health (NIH) under grant number R01 GM-107293. Some strains were provided by the Caenorhabditis Genetics Center, which is funded by the NIH Office of Research Infrastructure Programs (P40 OD-010440). The mass spectrometry was funded in part by an NYU School of Medicine Laura and Isaac Perlmutter Cancer Center grant from the National Cancer Institute (P30 CA-016087), and a shared instrumentation grant for an Orbitrap Fusion Lumos (1S10 OD-010582-01A1).

Publisher Copyright:
© 2019 by the Genetics Society of America.

Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.

Keywords

  • C. elegans
  • Chromatin
  • Condensin
  • Dosage compensation
  • Gene expression
  • Gene regulation
  • Histone modifications
  • Transcription
  • X chromosome

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