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

Ullah, I.; Thoelken, C.; Zhong, Y.; John, M.; Rossbach, O.; Lenz, J.; Goessringer, M.; Nist, A.; Stiewe, T.; Hartmann, R.; Vazquez, O.; Chung, H.-R.; Mackay, J.; Brehm, A.

doi:10.1101/2021.06.03.446896

bioRxiv · 10.1101/2021.06.03.446896

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

Ullah, I.·Thoelken, C.·Zhong, Y.·John, M.·Rossbach, O.·Lenz, J.·Goessringer, M.·Nist, A.·Stiewe, T.·Hartmann, R.·Vazquez, O.·Chung, H.-R.·Mackay, J.·Brehm, A.

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Abstract

The ATP-dependent nucleosome remodeller Mi-2/CHD4 broadly modulates epigenetic 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 previously undefined 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 remodeller 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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Ullah, I., Thoelken, C., Zhong, Y., John, M., Rossbach, O., Lenz, J., Goessringer, M., Nist, A., Stiewe, T., Hartmann, R., Vazquez, O., Chung, H.-R., Mackay, J., Brehm, A.. 2021-06-03. RNA inhibits dMi-2/CHD4 chromatin binding and nucleosome remodelling. https://doi.org/10.1101/2021.06.03.446896

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