Nuclear hormone receptor coregulator GRIP1 suppresses, whereas SRC1A and p/CIP coactivate, by domain-specific binding of MyoD.
p160 coregulators were initially identified as nuclear hormone receptor coactivators. In this study, functional data demonstrate that members of the three p160 families can have opposing roles in regulating gene expression by the same transcription factor. Both SRC1A and p/CIP function as coactivators for MyoD-mediated transcription whereas GRIP1 acts negatively as a (co)repressor. SRC1A and p/CIP predominantly interact with distinct sites on the NH2-terminal activation domain of MyoD. GRIP1 binds to both these regions but it alone, and neither SRC1A nor p/CIP, also interacts with specific sites on MyoD that are critical for the binding of the essential MyoD coactivator, p300. This suggests that competition by GRIP1 for SRC1A, p/CIP, and p300 binding sites on a transcription factor may regulate the activity of the factor.
Wu
Hung-Yi
HY
Institute for Genetic Medicine and Department of Biochemistry and Molecular Biology, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA.
Hamamori
Yasuo
Y
Xu
Jianming
J
Chang
Shin C
SC
Saluna
Terry
T
Chang
Ming-Fu
MF
O'Malley
Bert W
BW
Kedes
Larry
L
D000818:Animals; D001665:Binding Sites; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D017353:Gene Deletion; D005786:Gene Expression Regulation / Q000502:physiology; D051548:Histone Acetyltransferases; D051379:Mice; D008809:Mice, Inbred C3H; D017570:MyoD Protein / Q000737:chemistry / Q000235:genetics*; D056920:Nuclear Receptor Coactivator 1; D051958:Nuclear Receptor Coactivator 2; D056921:Nuclear Receptor Coactivator 3; D011401:Promoter Regions, Genetic / Q000502:physiology; D017434:Protein Structure, Tertiary; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D017570:MyoD Protein; C498002:Ncoa2 protein, mouse; D051958:Nuclear Receptor Coactivator 2; D015534:Trans-Activators; D014157:Transcription Factors; D051548:Histone Acetyltransferases; C538861:Ncoa1 protein, mouse; C538867:Ncoa3 protein, mouse; D056920:Nuclear Receptor Coactivator 1; D056921:Nuclear Receptor Coactivator 3