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Mol. Cell. Biol. doi:10.1128/MCB.00568-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

BAT3 and SET1A form a complex with CTCFL/BORIS to modulate H3K4 histone dimethylation and gene expression

Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; Institute of Genetic Medicine and Department of Medicine, and Departments of Molecular Biology and Genetics, and Oncology Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205; Johns Hopkins University School of Medicine, Baltimore, Maryland 21205; Pathology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892

^* To whom correspondence should be addressed. Email: afeinberg{at}jhu.edu. giusd{at}mail.nih.gov.

	Abstract

Chromatin status is characterized in part by covalent post-translational modifications of histones that regulate chromatin dynamics and direct gene expression. BORIS (brother of the regulator of imprinted sites) is an insulator DNA-binding protein thought to play a role in chromatin organization and gene expression. BORIS is a cancer-germline (CG) gene; these are genes normally present in male germ cells (testis) that are also expressed in cancer cell lines as well as primary tumors. This work identifies SET1A, a H3K4 methyltransferase, and BAT3, a co-chaperone recruiter, as binding partners for BORIS and these proteins bind to the upstream promoter regions of two well characterized pro-carcinogenic genes, Myc and BRCA1. RNAi knockdown of BAT3, as well as SET1A, decreased Myc and BRCA1 gene expression but did not affect the binding properties of BORIS, but RNAi knockdown of BORIS prevented the assembly of BAT3 and SET1A at the Myc and BRCA1 promoters. Finally, chromatin analysis suggested that BORIS and BAT3 exert their effects on gene expression by recruiting proteins like SET1A that are linked to changes in H3K4 dimethylation. Thus, we propose that BORIS acts as a platform upon which BAT3 and SET1A assemble and exert effects upon chromatin structure and gene expression.