A conserved 12-amino acid motif in Sall1 recruits the nucleosome remodeling and deacetylase corepressor complex.
Sall1 is a multi-zinc finger transcription factor that represses gene expression and regulates organogenesis. In this report, we further characterize the domain of Sall1 necessary for repression. We show that endogenous Sall1 binds to the nucleosome remodeling and deacetylase corepressor complex (NuRD) and confirm the functionality of the Sall1-associating macromolecular complex by showing that the complex possesses HDAC activity. NuRD is involved in global transcriptional repression and regulation of specific developmental processes. The mechanism by which sequence-specific DNA-binding proteins associate with NuRD is not well understood. We have identified a highly conserved 12-amino acid motif in the transcription factor Sall1 that is sufficient for the recruitment of NuRD. Single amino acid substitutions defined the critical amino acid peptide motif as RRKQXK-PXXF. This motif probably exhibits a more general role in regulating gene expression, since other proteins containing this domain, including all Sall family members and an unrelated zinc finger protein Ebfaz, mediate transcriptional repression and associate with NuRD. These results also have important implications for the pathogenesis of Townes-Brocks, a syndrome caused by SALL1 mutations.
Lauberth
Shannon M
SM
Department of Biochemistry and Molecular Biology, Veterans Affairs Medical Center, Saint Louis University, St. Louis, Missouri 63106, USA.
Rauchman
Michael
M
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D045744:Cell Line, Tumor; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000502:physiology; D006655:Histone Deacetylases / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex; D051379:Mice; D008969:Molecular Sequence Data; D010449:Peptide Mapping; D011485:Protein Binding; D012097:Repressor Proteins / Q000378:metabolism* / Q000502:physiology; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; C484557:Ebfaz protein, mouse; D012097:Repressor Proteins; C491254:Sall1 protein, mouse; D014157:Transcription Factors; D006655:Histone Deacetylases; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex