Bivalent recognition of nucleosomes by the tandem PHD fingers of the CHD4 ATPase is required for CHD4-mediated repression

Bivalent recognition of nucleosomes by the tandem PHD fingers of the CHD4 ATPase is required for CHD4-mediated repression. Musselman, C., Ramiŕez, J., Sims, J., Mansfield, R., Oliver, S., Denu, J., Mackay, J., Wade, P., Hagman, J., & Kutateladze, T. Proceedings of the National Academy of Sciences of the United States of America, 109(3):787-792, 2012. cited By 83

Paper doi abstract bibtex

CHD4 is a catalytic subunit of the NuRD (nucleosome remodeling and deacetylase) complex essential in transcriptional regulation, chromatin assembly and DNA damage repair. CHD4 contains tandem plant homeodomain (PHD) fingers connected by a short linker, the biological function of which remains unclear. Here we explore the combinatorial action of the CHD4 PHD1/2 fingers and detail the molecular basis for their association with chromatin. We found that PHD1/2 targets nucleosomes in a multivalent manner, concomitantly engaging two histone H3 tails. This robust synergistic interaction displaces HP1γ from pericentric sites, inducing changes in chromatin structure and leading to the dispersion of the heterochromatic mark H3K9me3. We demonstrate that recognition of the histone H3 tails by the PHD fingers is required for repressive activity of the CHD4/NuRD complex. Together, our data elucidate the molecular mechanism of multivalent association of the PHD fingers with chromatin and reveal their critical role in the regulation of CHD4 functions.

@ARTICLE{Musselman2012787,
author={Musselman, C.A. and Ramiŕez, J. and Sims, J.K. and Mansfield, R.E. and Oliver, S.S. and Denu, J.M. and Mackay, J.P. and Wade, P.A. and Hagman, J. and Kutateladze, T.G.},
title={Bivalent recognition of nucleosomes by the tandem PHD fingers of the CHD4 ATPase is required for CHD4-mediated repression},
journal={Proceedings of the National Academy of Sciences of the United States of America},
year={2012},
volume={109},
number={3},
pages={787-792},
doi={10.1073/pnas.1113655109},
note={cited By 83},
url={https://www.scopus.com/inward/record.uri?eid=2-s2.0-84856383786&doi=10.1073%2fpnas.1113655109&partnerID=40&md5=4d2a65c28bfef9051873d7efabd60bbd},
affiliation={Department of Pharmacology, University of Colorado Denver, School of Medicine, Aurora, CO 80045, United States; Integrated Department of Immunology, National Jewish Health, Denver, CO 80206, United States; Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, United States; School of Molecular Biosciences, University of Sydney, Sydney, NSW 2006, Australia; Department of Biomolecular Chemistry, University of Wisconsin, Madison, WI 53706, United States},
abstract={CHD4 is a catalytic subunit of the NuRD (nucleosome remodeling and deacetylase) complex essential in transcriptional regulation, chromatin assembly and DNA damage repair. CHD4 contains tandem plant homeodomain (PHD) fingers connected by a short linker, the biological function of which remains unclear. Here we explore the combinatorial action of the CHD4 PHD1/2 fingers and detail the molecular basis for their association with chromatin. We found that PHD1/2 targets nucleosomes in a multivalent manner, concomitantly engaging two histone H3 tails. This robust synergistic interaction displaces HP1γ from pericentric sites, inducing changes in chromatin structure and leading to the dispersion of the heterochromatic mark H3K9me3. We demonstrate that recognition of the histone H3 tails by the PHD fingers is required for repressive activity of the CHD4/NuRD complex. Together, our data elucidate the molecular mechanism of multivalent association of the PHD fingers with chromatin and reveal their critical role in the regulation of CHD4 functions.},
author_keywords={Epigenetics;  Gene repression;  Histone;  Posttranslational modifications},
keywords={adenosine triphosphatase;  chromodomain helicase DNA binding protein 4;  DNA binding protein;  heterochromatin protein 1;  histone deacetylase;  histone H3;  homeodomain protein;  unclassified drug, animal cell;  article;  chromatin;  controlled study;  dispersion;  molecular recognition;  nonhuman;  nucleosome;  priority journal, Amino Acid Sequence;  HEK293 Cells;  Heterochromatin;  Histones;  Homeodomain Proteins;  Humans;  Mi-2 Nucleosome Remodeling and Deacetylase Complex;  Models, Molecular;  Molecular Sequence Data;  Nucleosomes;  Protein Processing, Post-Translational;  Protein Structure, Tertiary;  Repressor Proteins;  Transcription, Genetic},
correspondence_address1={Kutateladze, T.G.; Department of Pharmacology, , Aurora, CO 80045, United States; email: Tatiana.Kutateladze@UCDenver.edu},
issn={00278424},
coden={PNASA},
pubmed_id={22215588},
language={English},
abbrev_source_title={Proc. Natl. Acad. Sci. U. S. A.},
document_type={Article},
source={Scopus},
}

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