NAB2 Represses Transcription by Interacting with the CHD4 Subunit of the Nucleosome Remodeling and Deacetylase (NuRD) Complex

Early growth response (EGR) transactivators act as critical regulators of several physiological processes, including peripheral nerve myelination and progression of prostate cancer. The NAB1 and NAB2 (NGFI-A/EGR1-binding protein) transcriptional corepressors directly interact with three EGR family m...

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Bibliographic Details
Published in:The Journal of biological chemistry 2006-06, Vol.281 (22), p.15129-15137
Main Authors: Srinivasan, Rajini, Mager, Gennifer M., Ward, Rebecca M., Mayer, Joshua, Svaren, John
Format: Article
Language:English
Subjects:
Alternative Splicing
Animals
Base Sequence
Binding Sites
Cell Line
DNA Helicases - metabolism
Histone Deacetylases - chemistry
Histone Deacetylases - genetics
Histone Deacetylases - metabolism
Humans
In Vitro Techniques
Male
Mi-2 Nucleosome Remodeling and Deacetylase Complex
Mice
Models, Biological
Neoplasm Proteins - chemistry
Neoplasm Proteins - genetics
Neoplasm Proteins - metabolism
Nucleosomes - metabolism
Promoter Regions, Genetic
Protein Structure, Tertiary
Protein Subunits
ras Proteins - genetics
Rats
Recombinant Proteins - chemistry
Recombinant Proteins - genetics
Recombinant Proteins - metabolism
Repressor Proteins - chemistry
Repressor Proteins - genetics
Repressor Proteins - metabolism
RNA, Messenger - genetics
RNA, Messenger - metabolism
Transcription, Genetic
Two-Hybrid System Techniques
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Summary:Early growth response (EGR) transactivators act as critical regulators of several physiological processes, including peripheral nerve myelination and progression of prostate cancer. The NAB1 and NAB2 (NGFI-A/EGR1-binding protein) transcriptional corepressors directly interact with three EGR family members (Egr1/NGFI-A/zif268, Egr2/Krox20, and Egr3) and repress activation of their target promoters. To understand the molecular mechanisms underlying NAB repression, we found that EGR activity is modulated by at least two repression domains within NAB2, one of which uniquely requires interaction with the CHD4 (chromodomain helicase DNA-binding protein 4) subunit of the NuRD (nucleosome remodeling and deacetylase) chromatin remodeling complex. Both NAB proteins can bind either CHD3 or CHD4, indicating that the interaction is conserved among these two protein families. Furthermore, we show that repression of the endogenous Rad gene by NAB2 involves interaction with CHD4 and demonstrate colocalization of NAB2 and CHD4 on the Rad promoter in myelinating Schwann cells. Finally, we show that interaction with CHD4 is regulated by alternative splicing of the NAB2 mRNA.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M600775200