4.8 Article

RNA inhibits dMi-2/CHD4 chromatin binding and nucleosome remodeling

Journal

CELL REPORTS
Volume 39, Issue 9, Pages -

Publisher

CELL PRESS
DOI: 10.1016/j.celrep.2022.110895

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Funding

  1. DFG [TRR81/A01]
  2. NHMRC [APP1126357]
  3. DFG Research Training Group (RTG) 2355 [325443116]

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This study discovered that the ATP-dependent nucleosome remodeler Mi-2/CHD4 interacts with thousands of mRNA molecules in vivo in Drosophila. It was also found that RNA inhibits the activity of Mi-2/CHD4 by competing with the nucleosome substrate, thereby protecting actively transcribed regions of the genome.
The ATP-dependent nucleosome remodeler Mi-2/CHD4 broadly modulates chromatin landscapes to repress transcription and to maintain genome integrity. Here we use individual nucleotide resolution crosslinking and immunoprecipitation (iCLIP) to show that Drosophila Mi-2 associates with thousands of mRNA molecules in vivo. Biochemical data reveal that recombinant dMi-2 preferentially binds to G-rich RNA molecules using two intrinsically disordered regions of unclear function. Pharmacological inhibition of transcription and RNase digestion approaches establish that RNA inhibits the association of dMi-2 with chromatin. We also show that RNA inhibits dMi-2-mediated nucleosome mobilization by competing with the nucleosome substrate. Importantly, this activity is shared by CHD4, the human homolog of dMi-2, strongly suggesting that RNA-mediated regulation of remodeler activity is an evolutionary conserved mechanism. Our data support a model in which RNA serves to protect actively transcribed regions of the genome from dMi-2/CHD4-mediated establishment of repressive chromatin structures.

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