The ubiquitin carboxyl hydrolase BAP1 forms a ternary complex with YY1 and HCF-1 and is a critical regulator of gene expression

Helen Yu, Nazar Mashtalir, Salima Daou, Ian Hammond-Martel, Julie Ross, Guangchao Sui, Gerald Warren Hart, Frank J. Rauscher, Elliot Drobetsky, Eric Milot, Yang Shi, El Bachir Affar

Research output: Contribution to journalArticle

Abstract

The candidate tumor suppressor BAP1 is a deubiquitinating enzyme (DUB) involved in the regulation of cell proliferation, although the molecular mechanisms governing its function remain poorly defined. BAP1 was recently shown to interact with and deubiquitinate the transcriptional regulator host cell factor 1 (HCF-1). Here we show that BAP1 assembles multiprotein complexes containing numerous transcription factors and cofactors, including HCF-1 and the transcription factor Yin Yang 1 (YY1). Through its coiled-coil motif, BAP1 directly interacts with the zinc fingers of YY1. Moreover, HCF-1 interacts with the middle region of YY1 encompassing the glycine-lysine-rich domain and is essential for the formation of a ternary complex with YY1 and BAP1 in vivo. BAP1 activates transcription in an enzymatic-activity-dependent manner and regulates the expression of a variety of genes involved in numerous cellular processes. We further show that BAP1 and HCF-1 are recruited by YY1 to the promoter of the cox7c gene, which encodes a mitochondrial protein used here as a model of BAP1-activated gene expression. Our findings (i) establish a direct link between BAP1 and the transcriptional control of genes regulating cell growth and proliferation and (ii) shed light on a novel mechanism of transcription regulation involving ubiquitin signaling.

Original languageEnglish (US)
Pages (from-to)5071-5085
Number of pages15
JournalMolecular and Cellular Biology
Volume30
Issue number21
DOIs
StatePublished - 2010

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology
  • Medicine(all)

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    Yu, H., Mashtalir, N., Daou, S., Hammond-Martel, I., Ross, J., Sui, G., Hart, G. W., Rauscher, F. J., Drobetsky, E., Milot, E., Shi, Y., & Affar, E. B. (2010). The ubiquitin carboxyl hydrolase BAP1 forms a ternary complex with YY1 and HCF-1 and is a critical regulator of gene expression. Molecular and Cellular Biology, 30(21), 5071-5085. https://doi.org/10.1128/MCB.00396-10