Ullah, I., Thölken, C., Zhong, Y., John, M., Rossbach, O., Lenz, J., Gößringer, M., Nist, A., Albert, L., Stiewe, T., Hartmann, R., Vázquez, O., Chung, H.R., Mackay, J.P., Brehm, A. (2022). RNA inhibits dMi-2/CHD4 chromatin binding and nucleosome remodeling.  Cell Rep. 39(9): 110895.

FBrf0253677

Research paper

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.