The engagement of histone lysine methyltransferases with nucleosomes: structural basis, regulatory mechanisms, and therapeutic implications

Histone lysine methyltransferases (HKMTs) deposit methyl groups onto lysine residues on histones and play important roles in regulating chromatin structure and gene expression. The structures and functions of HKMTs have been extensively investigated in recent decades, significantly advancing our und...

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Autores principales: Li, Yanjing, Ge, Kexue, Li, Tingting, Cai, Run, Chen, Yong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Review
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10098044/
https://www.ncbi.nlm.nih.gov/pubmed/37051671
http://dx.doi.org/10.1093/procel/pwac032
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author Li, Yanjing
Ge, Kexue
Li, Tingting
Cai, Run
Chen, Yong
author_facet Li, Yanjing
Ge, Kexue
Li, Tingting
Cai, Run
Chen, Yong
author_sort Li, Yanjing
collection PubMed
description Histone lysine methyltransferases (HKMTs) deposit methyl groups onto lysine residues on histones and play important roles in regulating chromatin structure and gene expression. The structures and functions of HKMTs have been extensively investigated in recent decades, significantly advancing our understanding of the dynamic regulation of histone methylation. Here, we review the recent progress in structural studies of representative HKMTs in complex with nucleosomes (H3K4, H3K27, H3K36, H3K79, and H4K20 methyltransferases), with emphasis on the molecular mechanisms of nucleosome recognition and trans-histone crosstalk by these HKMTs. These structural studies inform HKMTs’ roles in tumorigenesis and provide the foundations for developing new therapeutic approaches targeting HKMTs in cancers.
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spelling pubmed-100980442023-04-14 The engagement of histone lysine methyltransferases with nucleosomes: structural basis, regulatory mechanisms, and therapeutic implications Li, Yanjing Ge, Kexue Li, Tingting Cai, Run Chen, Yong Protein Cell Review Histone lysine methyltransferases (HKMTs) deposit methyl groups onto lysine residues on histones and play important roles in regulating chromatin structure and gene expression. The structures and functions of HKMTs have been extensively investigated in recent decades, significantly advancing our understanding of the dynamic regulation of histone methylation. Here, we review the recent progress in structural studies of representative HKMTs in complex with nucleosomes (H3K4, H3K27, H3K36, H3K79, and H4K20 methyltransferases), with emphasis on the molecular mechanisms of nucleosome recognition and trans-histone crosstalk by these HKMTs. These structural studies inform HKMTs’ roles in tumorigenesis and provide the foundations for developing new therapeutic approaches targeting HKMTs in cancers. Oxford University Press 2022-07-27 /pmc/articles/PMC10098044/ /pubmed/37051671 http://dx.doi.org/10.1093/procel/pwac032 Text en ©The Author(s) 2022. Published by Oxford University Press on behalf of Higher Education Press. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review
Li, Yanjing
Ge, Kexue
Li, Tingting
Cai, Run
Chen, Yong
The engagement of histone lysine methyltransferases with nucleosomes: structural basis, regulatory mechanisms, and therapeutic implications
title The engagement of histone lysine methyltransferases with nucleosomes: structural basis, regulatory mechanisms, and therapeutic implications
title_full The engagement of histone lysine methyltransferases with nucleosomes: structural basis, regulatory mechanisms, and therapeutic implications
title_fullStr The engagement of histone lysine methyltransferases with nucleosomes: structural basis, regulatory mechanisms, and therapeutic implications
title_full_unstemmed The engagement of histone lysine methyltransferases with nucleosomes: structural basis, regulatory mechanisms, and therapeutic implications
title_short The engagement of histone lysine methyltransferases with nucleosomes: structural basis, regulatory mechanisms, and therapeutic implications
title_sort engagement of histone lysine methyltransferases with nucleosomes: structural basis, regulatory mechanisms, and therapeutic implications
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10098044/
https://www.ncbi.nlm.nih.gov/pubmed/37051671
http://dx.doi.org/10.1093/procel/pwac032
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