ZMYND8 Co-localizes with NuRD on Target Genes and Regulates Poly(ADP-Ribose)-Dependent Recruitment of GATAD2A/NuRD to Sites of DNA Damage
Publication date
2016-10-11
Authors
Spruijt, Cornelia G
Luijsterburg, Martijn S
Menafra, Roberta
Lindeboom, Rik G H
Jansen, Pascal W T C
Edupuganti, Raghu Ram
Baltissen, Marijke P
Wiegant, Wouter W
Voelker-Albert, Moritz C
Matarese, Filomena
Editors
Advisors
Supervisors
Document Type
Article
Metadata
Show full item recordCollections
License
cc_by
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.
Keywords
Amino Acid Sequence, DNA Damage/genetics, DNA Repair/genetics, Enhancer Elements, Genetic/genetics, GATA Transcription Factors/metabolism, Genome, Human, HEK293 Cells, HeLa Cells, Humans, Mi-2 Nucleosome Remodeling and Deacetylase Complex/metabolism, Poly Adenosine Diphosphate Ribose/metabolism, Promoter Regions, Genetic, Protein Binding, Protein Domains, Protein Interaction Domains and Motifs, Protein Subunits/chemistry, Repressor Proteins, Tumor Suppressor Proteins/chemistry, Journal Article
Citation
Spruijt, C G, Luijsterburg, M S, Menafra, R, Lindeboom, R G H, Jansen, P W T C, Edupuganti, R R, Baltissen, M P, Wiegant, W W, Voelker-Albert, M C, Matarese, F, Mensinga, A, Poser, I, Vos, H R, Stunnenberg, H G, van Attikum, H & Vermeulen, M 2016, 'ZMYND8 Co-localizes with NuRD on Target Genes and Regulates Poly(ADP-Ribose)-Dependent Recruitment of GATAD2A/NuRD to Sites of DNA Damage', Cell Reports, vol. 17, no. 3, pp. 783-798. https://doi.org/10.1016/j.celrep.2016.09.037