High-resolution mapping defines the cooperative architecture of Polycomb response elements
- Guillermo A. Orsi1,2,
- Sivakanthan Kasinathan3,4,
- Kelly T. Hughes5,
- Sarah Saminadin-Peter1,
- Steven Henikoff3,6 and
- Kami Ahmad1,7
- 1Department of Biological Chemistry & Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA;
- 2CNRS–UMR218/Institut Curie, Centre de Recherche, Paris F-75248, France;
- 3Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA;
- 4Medical Scientist Training Program and Molecular & Cellular Biology Graduate Program, University of Washington, Seattle, Washington 98195, USA;
- 5Department of Molecular Genetics & Microbiology Graduate Program, Duke University Medical Center, Durham, North Carolina 27710, USA;
- 6Howard Hughes Medical Institute, Seattle, Washington 98109, USA
Abstract
Polycomb-mediated chromatin repression modulates gene expression during development in metazoans. Binding of multiple sequence-specific factors at discrete Polycomb response elements (PREs) is thought to recruit repressive complexes that spread across an extended chromatin domain. To dissect the structure of PREs, we applied high-resolution mapping of nonhistone chromatin proteins in native chromatin of Drosophila cells. Analysis of occupied sites reveal interactions between transcription factors that stabilize Polycomb anchoring to DNA, and implicate the general transcription factor ADF1 as a novel PRE component. By comparing two Drosophila cell lines with differential chromatin states, we provide evidence that repression is accomplished by enhanced Polycomb recruitment both to PREs and to target promoters of repressed genes. These results suggest that the stability of multifactor complexes at promoters and regulatory elements is a crucial aspect of developmentally regulated gene expression.
Footnotes
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↵7 Corresponding author
E-mail kami_ahmad{at}hms.harvard.edu
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.163642.113.
- Received July 17, 2013.
- Accepted January 30, 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/.
