Abstract
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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Differentiation
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Chromatin Immunoprecipitation
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DNA-Binding Proteins / physiology*
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Forkhead Transcription Factors / genetics*
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Forkhead Transcription Factors / metabolism
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Forkhead Transcription Factors / physiology*
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Gene Expression Regulation, Developmental*
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Heart / physiology
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Heart Septal Defects / pathology*
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Humans
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Immunoprecipitation
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Macrophages / cytology
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Macrophages / metabolism
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Mice
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Mice, Knockout
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Mice, Transgenic
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Monocytes / cytology
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Monocytes / metabolism
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Nuclear Receptor Co-Repressor 2
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Receptor, Macrophage Colony-Stimulating Factor / genetics
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Receptor, Macrophage Colony-Stimulating Factor / metabolism
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Repressor Proteins / genetics*
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Repressor Proteins / metabolism
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Repressor Proteins / physiology*
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Reverse Transcriptase Polymerase Chain Reaction
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Transcriptional Activation
Substances
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DNA-Binding Proteins
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FOXP1 protein, human
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Forkhead Transcription Factors
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Foxp1 protein, mouse
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NCOR2 protein, human
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Ncor2 protein, mouse
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Nuclear Receptor Co-Repressor 2
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RNA, Messenger
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Repressor Proteins
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Receptor, Macrophage Colony-Stimulating Factor