ZMYND8 co-localizes with NuRD on target genes and regulates recruitment of GATAD2A/NuRD to sites of DNA damage [RNA-seq]

The NuRD complex is generally thought to repress transcription at both hyper- and hypomethylated regions in the genome. In addition, the complex is involved in the DNA damage response. Here, we show that ZMYND8 bridges NuRD to a number of putative DNA-binding zinc finger proteins. The ZMYND8 MYND domain directly interacts with PPPL? motifs in the NuRD subunit GATAD2A. Furthermore, GATAD2A and GATAD2B exclusively form homodimers and they thus define mutually exclusive NuRD subcomplexes. ZMYND8 and MBD3 share a large number of genome-wide binding sites, mostly active promoters and enhancers. Depletion of ZMYND8 does not affect NuRD occupancy genome-wide and expression of NuRD/ZMYND8 target genes in steady-state asynchronous cells. However, ZMYND8 facilitates immediate recruitment of GATAD2A/NuRD to induced sites of DNA damage. These results thus show that a specific substoichiometric interaction with a NuRD subunit paralogue provides unique functionality to a distinct NuRD subcomplex. Overall design: RNA-seq samples for HeLa FRT-TO mock, ZMYND8KO, and ZMYND8KO-rescue cells

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Spruijt CG, Luijsterburg MS, Menafra R, Lindeboom RG, Jansen PW, Edupuganti RR, Baltissen MP, Wiegant WW, Voelker-Albert MC, Matarese F, Mensinga A, Poser I, Vos HR, Stunnenberg HG, van Attikum H, Vermeulen M