PT  - JOURNAL ARTICLE
AU  - Ikram Ullah
AU  - Clemens Thoelken
AU  - Yichen Zhong
AU  - Mara John
AU  - Oliver Rossbach
AU  - Jonathan Lenz
AU  - Markus Großringer
AU  - Andrea Nist
AU  - Thorsten Stiewe
AU  - Roland Hartmann
AU  - Olalla Vazquez
AU  - Ho-Ryung Chung
AU  - Joel P Mackay
AU  - Alexander Brehm
TI  - RNA inhibits dMi-2/CHD4 chromatin binding and nucleosome remodelling
AID  - 10.1101/2021.06.03.446896
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.06.03.446896
4099  - http://biorxiv.org/content/early/2021/06/03/2021.06.03.446896.short
4100  - http://biorxiv.org/content/early/2021/06/03/2021.06.03.446896.full
AB  - 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.Competing Interest StatementThe authors have declared no competing interest.