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PMID: 23752268 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

The functional interactome landscape of the human histone deacetylase family.

Molecular systems biology ·Vol. 9 ·2013-00-00 ·Pages 672

Joshi P, Greco TM, Guise AJ, Luo Y, Yu F, Nesvizhskii AI, Cristea IM

Abstract

Histone deacetylases (HDACs) are a diverse family of essential transcriptional regulatory enzymes, that function through the spatial and temporal recruitment of protein complexes. As the composition and regulation of HDAC complexes are only partially characterized, we built the first global protein interaction network for all 11 human HDACs in T cells. Integrating fluorescence microscopy, immunoaffinity purifications, quantitative mass spectrometry, and bioinformatics, we identified over 200 unreported interactions for both well-characterized and lesser-studied HDACs, a subset of which were validated by orthogonal approaches. We establish HDAC11 as a member of the survival of motor neuron complex and pinpoint a functional role in mRNA splicing. We designed a complementary label-free and metabolic-labeling mass spectrometry-based proteomics strategy for profiling interaction stability among different HDAC classes, revealing that HDAC1 interactions within chromatin-remodeling complexes are largely stable, while transcription factors preferentially exist in rapid equilibrium. Overall, this study represents a valuable resource for investigating HDAC functions in health and disease, encompassing emerging themes of HDAC regulation in cell cycle and RNA processing and a deeper functional understanding of HDAC complex stability.

MeSH Terms
Cell Cycle/genetics Chromatin Assembly and Disassembly Gene Expression Profiling Gene Expression Regulation Histone Deacetylase 1/genetics,metabolism Histone Deacetylases/genetics,metabolism Humans Protein Folding Protein Interaction Maps RNA Splicing SMN Complex Proteins/genetics,metabolism Signal Transduction T-Lymphocytes/cytology,metabolism Transcription Factors/genetics,metabolism
Chemicals
SMN Complex Proteins Transcription Factors HDAC1 protein, human HDAC11 protein, human Histone Deacetylase 1 Histone Deacetylases
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Joshi Preeti
Department of Molecular Biology, Princeton University, Princeton, NJ, USA.
Greco Todd M
Guise Amanda J
Luo Yang
Yu Fang
Nesvizhskii Alexey I
Cristea Ileana M
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Article Info
Journal
Molecular systems biology
Abbr.
Mol Syst Biol
ISSN
1744-4292
DOI
10.1038/msb.2013.26
Published
2013-00-00
Pages
672
Language
English
Region
England
NLM ID
101235389
PMCID
PMC3964310
Subset
IM
Grants
NIDA NIH HHS · DP1 DA026192 · United States
NIDA NIH HHS · DP1DA026192 · United States
NIAID NIH HHS · R21 AI102187 · United States
NIGMS NIH HHS · R01 GM094231 · United States
NIGMS NIH HHS · R01GM094231 · United States
NIAID NIH HHS · R21AI102187 · United States
Corrections
CommentIn
PMID: 23752267
External Links
PubMed source DOI: 10.1038/msb.2013.26 PMC Full Text View journal details
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