USP44 Is an Integral Component of N-CoR that Contributes to Gene Repression by Deubiquitinating Histone H2B

Xianjiang Lan, Boyko S. Atanassov, Wenqian Li, Ying Zhang, Laurence Florens, Ryan D. Mohan, Paul J. Galardy, Michael P. Washburn, Jerry L. Workman, Sharon Y R Dent

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Decreased expression of the USP44 deubiquitinase has been associated with global increases in H2Bub1 levels during mouse embryonic stem cell (mESC) differentiation. However, whether USP44 directly deubiquitinates histone H2B or how its activity is targeted to chromatin is not known. We identified USP44 as an integral subunit of the nuclear receptor co-repressor (N-CoR) complex. USP44 within N-CoR deubiquitinates H2B in vitro and in vivo, and ablation of USP44 impairs the repressive activity of the N-CoR complex. Chromatin immunoprecipitation (ChIP) experiments confirmed that USP44 recruitment reduces H2Bub1 levels at N-CoR target loci. Furthermore, high expression of USP44 correlates with reduced levels of H2Bub1 in the breast cancer cell line MDA-MB-231. Depletion of either USP44 or TBL1XR1 impairs the invasiveness of MDA-MB-231 cells in vitro and causes an increase of global H2Bub1 levels. Our findings indicate that USP44 contributes to N-CoR functions in regulating gene expression and is required for efficient invasiveness of triple-negative breast cancer cells.

Original languageEnglish (US)
Pages (from-to)2382-2393
Number of pages12
JournalCell Reports
Volume17
Issue number9
DOIs
StatePublished - Nov 22 2016

Fingerprint

Co-Repressor Proteins
Histones
Genes
Chromatin
Cells
Triple Negative Breast Neoplasms
Chromatin Immunoprecipitation
Ablation
Stem cells
Gene expression
Cell Differentiation
Breast Neoplasms
Gene Expression
Cell Line
Experiments

Keywords

  • breast cancer
  • H2B ubiquitination
  • N-CoR
  • transcription
  • USP44

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Lan, X., Atanassov, B. S., Li, W., Zhang, Y., Florens, L., Mohan, R. D., ... Dent, S. Y. R. (2016). USP44 Is an Integral Component of N-CoR that Contributes to Gene Repression by Deubiquitinating Histone H2B. Cell Reports, 17(9), 2382-2393. https://doi.org/10.1016/j.celrep.2016.10.076

USP44 Is an Integral Component of N-CoR that Contributes to Gene Repression by Deubiquitinating Histone H2B. / Lan, Xianjiang; Atanassov, Boyko S.; Li, Wenqian; Zhang, Ying; Florens, Laurence; Mohan, Ryan D.; Galardy, Paul J.; Washburn, Michael P.; Workman, Jerry L.; Dent, Sharon Y R.

In: Cell Reports, Vol. 17, No. 9, 22.11.2016, p. 2382-2393.

Research output: Contribution to journalArticle

Lan, X, Atanassov, BS, Li, W, Zhang, Y, Florens, L, Mohan, RD, Galardy, PJ, Washburn, MP, Workman, JL & Dent, SYR 2016, 'USP44 Is an Integral Component of N-CoR that Contributes to Gene Repression by Deubiquitinating Histone H2B', Cell Reports, vol. 17, no. 9, pp. 2382-2393. https://doi.org/10.1016/j.celrep.2016.10.076
Lan, Xianjiang ; Atanassov, Boyko S. ; Li, Wenqian ; Zhang, Ying ; Florens, Laurence ; Mohan, Ryan D. ; Galardy, Paul J. ; Washburn, Michael P. ; Workman, Jerry L. ; Dent, Sharon Y R. / USP44 Is an Integral Component of N-CoR that Contributes to Gene Repression by Deubiquitinating Histone H2B. In: Cell Reports. 2016 ; Vol. 17, No. 9. pp. 2382-2393.
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