Cross-talk between Lysine-Modifying Enzymes Controls Site-Specific DNA Amplifications.

Authors:
Sweta Mishra
Sweta Mishra
University of Texas Health Science Center
United States
Sangita Pal
Sangita Pal
The University of Texas at El Paso
United States
Thomas L Clarke
Thomas L Clarke
University of Central Florida
United States
Damayanti Chakraborty
Damayanti Chakraborty
Institute for Reproductive Health and Regenerative Medicine
Joshua C Black
Joshua C Black
Harvard Medical School
United States
Sedona E Murphy
Sedona E Murphy
Harvard Medical School

Cell 2018 Aug 26;174(4):803-817.e16. Epub 2018 Jul 26.

Massachusetts General Hospital Cancer Center and Department of Medicine, Harvard Medical School, 13(th) Street, Charlestown, MA 02129, USA. Electronic address:

Acquired chromosomal DNA amplifications are features of many tumors. Although overexpression and stabilization of the histone H3 lysine 9/36 (H3K9/36) tri-demethylase KDM4A generates transient site-specific copy number gains (TSSGs), additional mechanisms directly controlling site-specific DNA copy gains are not well defined. In this study, we uncover a collection of H3K4-modifying chromatin regulators that function with H3K9 and H3K36 regulators to orchestrate TSSGs. Specifically, the H3K4 tri-demethylase KDM5A and specific COMPASS/KMT2 H3K4 methyltransferases modulate different TSSG loci through H3K4 methylation states and KDM4A recruitment. Furthermore, a distinct chromatin modifier network, MLL1-KDM4B-KDM5B, controls copy number regulation at a specific genomic locus in a KDM4A-independent manner. These pathways comprise an epigenetic addressing system for defining site-specific DNA rereplication and amplifications.

Abstract Video

Control of Transient Genomic Instability / Cell, August 9, 2018 (Vol. 174, iss. 4)


Source: Cell Press

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Source
http://dx.doi.org/10.1016/j.cell.2018.06.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6212369PMC

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August 2018
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