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Updated: Sep 21, 2025
10:28
Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
Published on: September 20, 2018
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RNA inhibits dMi-2/CHD4 chromatin binding and nucleosome remodeling
Ikram Ullah1, Clemens Thölken2, Yichen Zhong3
1Institute of Molecular Biology and Tumor Research, Biomedical Research Center, Philipps-University, Marburg, Germany.
Cell Reports
|June 1, 2022
Summary
The ATP-dependent nucleosome remodeler Mi-2/CHD4 binds to mRNA. RNA inhibits Mi-2/CHD4
Area of Science:
- Molecular Biology
- Epigenetics
- Chromatin Biology
Background:
- The Mi-2/CHD4 complex is an ATP-dependent nucleosome remodeler.
- It plays a crucial role in transcription repression and genome stability.
Purpose of the Study:
- To investigate the interaction of Drosophila Mi-2 with RNA in vivo.
- To elucidate the mechanism by which RNA regulates Mi-2/CHD4 activity.
Main Methods:
- Individual nucleotide resolution crosslinking and immunoprecipitation (iCLIP).
- Biochemical binding assays with recombinant dMi-2.
- Pharmacological inhibition of transcription and RNase digestion.
Main Results:
- Drosophila Mi-2 (dMi-2) associates with thousands of mRNA molecules in vivo.
- Recombinant dMi-2 preferentially binds to G-rich RNA sequences.
- RNA inhibits dMi-2 binding to chromatin and nucleosome mobilization.
- This RNA-mediated inhibition is conserved in human CHD4.
Conclusions:
- RNA acts as a negative regulator of Mi-2/CHD4 activity.
- RNA binding prevents Mi-2/CHD4 from establishing repressive chromatin structures in actively transcribed regions.
- RNA-mediated regulation of nucleosome remodelers is an evolutionarily conserved mechanism.
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