Histone H4K16ac Binding Function of the Triple PHD Finger Cassette of MLL4.

Autor: Kumar Sinha V; Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA., Zhang Y; Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA., Xu L; Department of Epigenetics, Van Andel Institute, Grand Rapids, MI 49503, USA., Chen YW; Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan., Picaud S; Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX3 7DQ, UK., Zandian M; Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA., Biswas S; Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA., Filippakopoulos P; Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX3 7DQ, UK., Wang SP; Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan., Shi X; Department of Epigenetics, Van Andel Institute, Grand Rapids, MI 49503, USA., Kutateladze TG; Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA. Electronic address: tatiana.kutateladze@cuanschutz.edu.
Jazyk: angličtina
Zdroj: Journal of molecular biology [J Mol Biol] 2024 Apr 01; Vol. 436 (7), pp. 168212. Date of Electronic Publication: 2023 Jul 20.
DOI: 10.1016/j.jmb.2023.168212
Abstrakt: The human methyltransferase MLL4 plays a critical role in embryogenesis and development, and aberrant activity of MLL4 is linked to neurodegenerative and developmental disorders and cancer. MLL4 contains the catalytic SET domain that catalyzes mono methylation of lysine 4 of histone H3 (H3K4me1) and seven plant homeodomain (PHD) fingers, six of which have not been structurally and functionally characterized. Here, we demonstrate that the triple PHD finger cassette of MLL4, harboring its fourth, fifth and sixth PHD fingers (MLL4 PHD456 ) forms an integrated module, maintains the binding selectivity of the PHD6 finger toward acetylated lysine 16 of histone H4 (H4K16ac), and is capable of binding to DNA. Our findings highlight functional correlation between H4K16ac and H3K4me1, two major histone modifications that are recognized and written, respectively, by MLL4.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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