Epigenetic therapies targeting histone lysine methylation: complex mechanisms and clinical challenges

S Gold, A Shilatifard - The Journal of Clinical Investigation, 2024 - jci.org
As epigenetic therapies continue to gain ground as potential treatment strategies for cancer
and other diseases, compounds that target histone lysine methylation and the enzyme …

[HTML][HTML] Navigating the complexity of Polycomb repression: Enzymatic cores and regulatory modules

S Tamburri, S Rustichelli, S Amato, D Pasini - Molecular Cell, 2024 - cell.com
Polycomb proteins are a fundamental repressive system that plays crucial developmental
roles by orchestrating cell-type-specific transcription programs that govern cell identity …

Cancer-associated DNA hypermethylation of Polycomb targets requires DNMT3A dual recognition of histone H2AK119 ubiquitination and the nucleosome acidic …

KH Gretarsson, S Abini-Agbomson, SL Gloor… - Science …, 2024 - science.org
During tumor development, promoter CpG islands that are normally silenced by Polycomb
repressive complexes (PRCs) become DNA-hypermethylated. The molecular mechanism by …

Structural and mechanistic basis for nucleosomal H2AK119 deubiquitination by single-subunit deubiquitinase USP16

H Ai, Z He, Z Deng, GC Chu, Q Shi, Z Tong… - Nature Structural & …, 2024 - nature.com
Epigenetic regulators have a crucial effect on gene expression based on their manipulation
of histone modifications. Histone H2AK119 monoubiquitination (H2AK119Ub), a well …

Nucleosome conformation dictates the histone code

MR Marunde, HA Fuchs, JM Burg, IK Popova, A Vaidya… - Elife, 2024 - elifesciences.org
Histone post-translational modifications (PTMs) play a critical role in chromatin regulation. It
has been proposed that these PTMs form localized 'codes' that are read by specialized …

Beyond the tail: the consequence of context in histone post-translational modification and chromatin research

EN Weinzapfel, KN Fedder-Semmes… - Biochemical …, 2024 - portlandpress.com
The role of histone post-translational modifications (PTMs) in chromatin structure and
genome function has been the subject of intense debate for more than 60 years. Though …

Read–write mechanisms of H2A ubiquitination by Polycomb repressive complex 1

VG López, MI Valencia-Sánchez, S Abini-Agbomson… - Nature, 2024 - nature.com
Epigenetic inheritance of silent chromatin domains is fundamental to cellular memory during
embryogenesis, but it must overcome the dilution of repressive histone modifications during …

[HTML][HTML] DoUBLing up: ubiquitin and ubiquitin-like proteases in genome stability

BM Foster, Z Wang, CK Schmidt - Biochemical Journal, 2024 - portlandpress.com
Maintaining stability of the genome requires dedicated DNA repair and signalling processes
that are essential for the faithful duplication and propagation of chromosomes. These DNA …

Differential modulation of polycomb-associated histone marks by cBAF, pBAF, and gBAF complexes

M Bergwell, JY Park, JG Kirkland - Life science alliance, 2024 - life-science-alliance.org
Chromatin regulators alter the physical properties of chromatin to make it more or less
permissive to transcription by modulating another protein's access to a specific DNA …

A mutant ASXL1-BAP1-EHMT complex contributes to heterochromatin dysfunction in clonal hematopoiesis and chronic monomyelocytic leukemia

Z Dong, H Sepulveda, LJ Arteaga-Vazquez… - Proceedings of the …, 2025 - pnas.org
ASXL transcriptional regulator 1 (ASXL1) is one of the three most frequently mutated genes
in age-related clonal hematopoiesis (CH), alongside DNA methyltransferase 3 alpha …