The preRC protein ORCA organizes heterochromatin by assembling histone H3 lysine 9 methyltransferases on chromatin
- University of Illinois at Urbana-Champaign, United States
- Centre National de la Recherche Scientifique, France
Abstract
Heterochromatic domains are enriched with repressive histone marks, including histone H3 lysine 9 methylation, written by lysine methyltransferases (KMTs). The pre-replication complex protein Origin Recognition Complex-Associated (ORCA/LRWD1) preferentially localizes to heterochromatic regions in post-replicated cells. Its role in heterochromatin organization remained elusive. ORCA recognizes methylated H3K9 marks and interacts with repressive KMTs, including G9a/GLP and Suv39H1 in a chromatin context-dependent manner. Single-molecule pull-down assays demonstrate that ORCA-ORC and multiple H3K9 KMTs exist in a single complex and that ORCA stabilizes H3K9 KMT complex. Cells lacking ORCA show alterations in chromatin architecture, with significantly reduced H3K9 di- and tri-methylation at specific chromatin sites. Changes in heterochromatin structure due to loss of ORCA affects replication timing, preferentially at the late-replicating regions. We demonstrate that ORCA acts as a scaffold for the establishment of H3K9 KMT complex and its association and activity at specific chromatin sites is crucial for the organization of heterochromatin structure.
Article and author information
Author details
Reviewing Editor
- Michael R Botchan, University of California, Berkeley, United States
Version history
- Received: January 15, 2015
- Accepted: April 27, 2015
- Accepted Manuscript published: April 29, 2015 (version 1)
- Version of Record published: May 26, 2015 (version 2)
Copyright
© 2015, Giri et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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The preRC protein ORCA organizes heterochromatin by assembling histone H3 lysine 9 methyltransferases on chromatin
eLife 4:e06496.
https://doi.org/10.7554/eLife.06496
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