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

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.

• 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.