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 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.
Srinivasan
Rajini
R
Department of Comparative Biosciences, University of Wisconsin, Madison, WI 53706, USA.
Mager
Gennifer M
GM
Ward
Rebecca M
RM
Mayer
Joshua
J
Svaren
John
J
D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D004265:DNA Helicases / Q000378:metabolism; D006655:Histone Deacetylases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex; D051379:Mice; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009707:Nucleosomes / Q000378:metabolism; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D021122:Protein Subunits; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D020798:Two-Hybrid System Techniques; D018631:ras Proteins / Q000235:genetics
C099945:Nab2 protein, mouse; D009363:Neoplasm Proteins; D009707:Nucleosomes; D021122:Protein Subunits; D012333:RNA, Messenger; D011994:Recombinant Proteins; D012097:Repressor Proteins; C490030:Rrad protein, mouse; D006655:Histone Deacetylases; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex; D004265:DNA Helicases; D018631:ras Proteins