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

doi:10.1016/j.celrep.2016.09.037

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

Cancer

Research output: Contribution to journal › Article › Academic › peer-review

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 language	English
Pages (from-to)	783-798
Number of pages	16
Journal	Cell Reports
Volume	17
Issue number	3
DOIs	https://doi.org/10.1016/j.celrep.2016.09.037
Publication status	Published - 11 Oct 2016

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

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1-s2.0-S2211124716312761-mainFinal published version, 16.1 MBLicence: CC BY

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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, 17(3), 783-798. https://doi.org/10.1016/j.celrep.2016.09.037

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

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",

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

year = "2016",

month = oct,

day = "11",

doi = "10.1016/j.celrep.2016.09.037",

language = "English",

volume = "17",

pages = "783--798",

journal = "Cell Reports",

issn = "2211-1247",

publisher = "Cell Press",

number = "3",

}

Spruijt, CG, Luijsterburg, MS, Menafra, R, Lindeboom, RGH, Jansen, PWTC, Edupuganti, RR, Baltissen, MP, Wiegant, WW, Voelker-Albert, MC, Matarese, F, Mensinga, A, Poser, I, Vos, HR, Stunnenberg, HG, 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

TY - JOUR

T1 - ZMYND8 Co-localizes with NuRD on Target Genes and Regulates Poly(ADP-Ribose)-Dependent Recruitment of GATAD2A/NuRD to Sites of DNA Damage

AU - Spruijt, Cornelia G

AU - Luijsterburg, Martijn S

AU - Menafra, Roberta

AU - Lindeboom, Rik G H

AU - Jansen, Pascal W T C

AU - Edupuganti, Raghu Ram

AU - Baltissen, Marijke P

AU - Wiegant, Wouter W

AU - Voelker-Albert, Moritz C

AU - Matarese, Filomena

AU - Mensinga, Anneloes

AU - Poser, Ina

AU - Vos, Harmjan R

AU - Stunnenberg, Hendrik G

AU - van Attikum, Haico

AU - Vermeulen, Michiel

PY - 2016/10/11

Y1 - 2016/10/11

N2 - 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.

AB - 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.

KW - Amino Acid Sequence

KW - DNA Damage/genetics

KW - DNA Repair/genetics

KW - Enhancer Elements, Genetic/genetics

KW - GATA Transcription Factors/metabolism

KW - Genome, Human

KW - HEK293 Cells

KW - HeLa Cells

KW - Humans

KW - Mi-2 Nucleosome Remodeling and Deacetylase Complex/metabolism

KW - Poly Adenosine Diphosphate Ribose/metabolism

KW - Promoter Regions, Genetic

KW - Protein Binding

KW - Protein Domains

KW - Protein Interaction Domains and Motifs

KW - Protein Subunits/chemistry

KW - Repressor Proteins

KW - Tumor Suppressor Proteins/chemistry

U2 - 10.1016/j.celrep.2016.09.037

DO - 10.1016/j.celrep.2016.09.037

M3 - Article

C2 - 27732854

SN - 2211-1247

VL - 17

SP - 783

EP - 798

JO - Cell Reports

JF - Cell Reports

IS - 3

ER -

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

Abstract

Keywords

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