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8Q1G

LSD1-CoREST bound to Acetylated K14 of Histone H3

Summary for 8Q1G
Entry DOI10.2210/pdb8q1g/pdb
DescriptorLysine-specific histone demethylase 1A, REST corepressor 1, Histone H3.3C, ... (5 entities in total)
Functional Keywordshistone code, demethylase, flavin, oxidoreductase
Biological sourceHomo sapiens (human)
More
Total number of polymer chains3
Total formula weight104614.51
Authors
Barone, M.,Mattevi, A. (deposition date: 2023-07-31, release date: 2024-05-15, Last modification date: 2024-11-06)
Primary citationLee, K.,Barone, M.,Waterbury, A.L.,Jiang, H.,Nam, E.,DuBois-Coyne, S.E.,Whedon, S.D.,Wang, Z.A.,Caroli, J.,Neal, K.,Ibeabuchi, B.,Dhoondia, Z.,Kuroda, M.I.,Liau, B.B.,Beck, S.,Mattevi, A.,Cole, P.A.
Uncoupling histone modification crosstalk by engineering lysine demethylase LSD1.
Nat.Chem.Biol., 2024
Cited by
PubMed Abstract: Biochemical crosstalk between two or more histone modifications is often observed in epigenetic enzyme regulation, but its functional significance in cells has been difficult to discern. Previous enzymatic studies revealed that Lys14 acetylation of histone H3 can inhibit Lys4 demethylation by lysine-specific demethylase 1 (LSD1). In the present study, we engineered a mutant form of LSD1, Y391K, which renders the nucleosome demethylase activity of LSD1 insensitive to Lys14 acetylation. K562 cells with the Y391K LSD1 CRISPR knockin show decreased expression of a set of genes associated with cellular adhesion and myeloid leukocyte activation. Chromatin profiling revealed that the cis-regulatory regions of these silenced genes display a higher level of H3 Lys14 acetylation, and edited K562 cells show diminished H3 mono-methyl Lys4 near these silenced genes, consistent with a role for enhanced LSD1 demethylase activity. These findings illuminate the functional consequences of disconnecting histone modification crosstalk for a key epigenetic enzyme.
PubMed: 38965385
DOI: 10.1038/s41589-024-01671-9
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (2.6 Å)
Structure validation

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PDB entries from 2024-11-06

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