Cooperative regulation in development by SMRT and FOXP1.
A critical aspect of mammalian development involves the actions of dedicated repressors/corepressors to prevent unregulated gene activation programs that would initiate specific cell determination events. While the role of NCoR/SMRT corepressors in nuclear receptor actions is well documented, we here report that a previously unrecognized functional interaction between SMRT and a forkhead protein, FOXP1, is required for cardiac growth and regulation of macrophage differentiation. Our studies demonstrate that SMRT and FOXP1 define a functional biological unit required to orchestrate specific programs critical for mammalian organogenesis, linking developmental roles of FOX to a specific corepressor.
Jepsen
Kristen
K
Department of Medicine, Howard Hughes Medical Institute, University of California at San Diego, School of Medicine, La Jolla, California 92093, USA. jepsen@ucsd.edu
Gleiberman
Anatoli S
AS
Shi
Can
C
Simon
Daniel I
DI
Rosenfeld
Michael G
MG
D000818:Animals; D002454:Cell Differentiation; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins / Q000502:physiology*; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000502:physiology; D006343:Heart Septal Defects / Q000473:pathology*; D006801:Humans; D047468:Immunoprecipitation; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D056985:Nuclear Receptor Co-Repressor 2; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; C486626:FOXP1 protein, human; D051858:Forkhead Transcription Factors; C432917:Foxp1 protein, mouse; C539130:NCOR2 protein, human; C539131:Ncor2 protein, mouse; D056985:Nuclear Receptor Co-Repressor 2; D012333:RNA, Messenger; D012097:Repressor Proteins; D016186:Receptor, Macrophage Colony-Stimulating Factor