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Updated: May 29, 2026
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Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
Published on: September 20, 2018
Gene repressive activity of RIP140 through direct interaction with CDK8
Shawna D Persaud1, Wei-Hong Huang, Sung Wook Park
1Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA.
Molecular Endocrinology (Baltimore, Md.)
|August 27, 2011
Summary
Receptor interacting protein 140 (RIP140) replaces TRAP220(MED1) on the CrabpI promoter during adipocyte differentiation. RIP140 interacts with CDK8, mediated by acetylation, to repress gene expression.
Area of Science:
- Molecular Biology
- Gene Regulation
- Epigenetics
Background:
- Receptor interacting protein 140 (RIP140) is a key gene repressor.
- Posttranslational modifications enhance RIP140 activity.
- RIP140 and TRAP220(MED1) have opposing roles in CrabpI gene regulation during adipocyte differentiation.
Purpose of the Study:
- To investigate the mechanism of RIP140 replacing TRAP220(MED1) on the CrabpI promoter.
- To explore the interaction between RIP140 and cyclin-dependent kinase 8 (CDK8).
- To elucidate the role of RIP140 acetylation in gene repression.
Main Methods:
- Chromatin immunoprecipitation assays to assess protein recruitment.
- Co-immunoprecipitation to study protein interactions.
- Site-directed mutagenesis and acetylation-mimetic mutations to analyze RIP140 function.
Main Results:
- RIP140 recruitment to the CrabpI promoter increases as TRAP220(MED1) recruitment decreases during T(3)-induced adipocyte differentiation.
- RIP140 directly interacts with CDK8 via its N-terminus, an interaction enhanced by lysine acetylation.
- Acetylated RIP140 more effectively recruits CDK8 and repressive factors like G9a, leading to stronger CrabpI gene repression.
Conclusions:
- RIP140 replaces TRAP220(MED1) on the CrabpI promoter during adipocyte differentiation.
- A novel mechanism of gene repression involving RIP140-CDK8 interaction, stimulated by RIP140 acetylation, is identified.
- This interaction facilitates the recruitment of repressive machinery, underscoring RIP140's role in transcriptional regulation.
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