ZMYND8 Co-localizes with NuRD on Target Genes and Regulates Poly(ADP-Ribose)-Dependent Recruitment of GATAD2A/NuRD to Sites of DNA Damage

Cornelia G. Spruijt, Martijn S. Luijsterburg, Roberta Menafra, Rik G.H. Lindeboom, Pascal W.T.C. Jansen, Raghu Ram Edupuganti, Marijke P. Baltissen, Wouter W. Wiegant, Moritz C. Voelker-Albert, Filomena Matarese, Anneloes Mensinga, Ina Poser, Harmjan R. Vos, Hendrik G. Stunnenberg, Haico van Attikum, Michiel Vermeulen

Research output: Contribution to journalArticlepeer-review

81 Citations (Scopus)

Abstract

NuRD (nucleosome remodeling and histone deacetylase) is a versatile multi-protein complex with roles in transcription regulation and the DNA damage response. Here, we show that ZMYND8 bridges NuRD to a number of putative DNA-binding zinc finger proteins. The MYND domain of ZMYND8 directly interacts with PPPLΦ motifs in the NuRD subunit GATAD2A. Both GATAD2A and GATAD2B exclusively form homodimers and define mutually exclusive NuRD subcomplexes. ZMYND8 and NuRD 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 only slightly affects expression of NuRD/ZMYND8 target genes. In contrast, the MYND domain in ZMYND8 facilitates the rapid, poly(ADP-ribose)-dependent recruitment of GATAD2A/NuRD to sites of DNA damage to promote repair by homologous recombination. Thus, these results show that a specific substoichiometric interaction with a NuRD subunit paralogue provides unique functionality to distinct NuRD subcomplexes.

Original languageEnglish
Pages (from-to)783-798
Number of pages16
JournalCell Reports
Volume17
Issue number3
DOIs
Publication statusPublished - 11 Oct 2016
Externally publishedYes

Keywords

  • chromatin
  • DNA damage
  • GATAD2A
  • gene expression
  • interaction proteomics
  • next-generation sequencing
  • NuRD
  • ZMYND8

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