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Lookup NU author(s): Rebecca Harris, Dr Maninder Heer, Dr Mark Levasseur, Dr Tyrell Cartwright, Beth Weston, Jennifer Mitchell, Dr Jonathan Coxhead, Dr Luke GaughanORCiD, Dr Lisa PrendergastORCiD, Professor Jonathan HigginsORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2023, The Author(s). Histone modifications influence the recruitment of reader proteins to chromosomes to regulate events including transcription and cell division. The idea of a histone code, where combinations of modifications specify unique downstream functions, is widely accepted and can be demonstrated in vitro. For example, on synthetic peptides, phosphorylation of Histone H3 at threonine-3 (H3T3ph) prevents the binding of reader proteins that recognize trimethylation of the adjacent lysine-4 (H3K4me3), including the TAF3 component of TFIID. To study these combinatorial effects in cells, we analyzed the genome-wide distribution of H3T3ph and H3K4me2/3 during mitosis. We find that H3T3ph anti-correlates with adjacent H3K4me2/3 in cells, and that the PHD domain of TAF3 can bind H3K4me2/3 in isolated mitotic chromatin despite the presence of H3T3ph. Unlike in vitro, H3K4 readers are still displaced from chromosomes in mitosis in Haspin-depleted cells lacking H3T3ph. H3T3ph is therefore unlikely to be responsible for transcriptional downregulation during cell division.
Author(s): Harris RJ, Heer M, Levasseur MD, Cartwright TN, Weston B, Mitchell JL, Coxhead JM, Gaughan L, Prendergast L, Rico D, Higgins JMG
Publication type: Article
Publication status: Published
Journal: Nature Communications
Year: 2023
Volume: 14
Online publication date: 09/11/2023
Acceptance date: 31/10/2023
Date deposited: 20/11/2023
ISSN (electronic): 2041-1723
Publisher: Springer Nature
URL: https://doi.org/10.1038/s41467-023-43115-3
DOI: 10.1038/s41467-023-43115-3
Data Access Statement: Raw and processed ChIP-seq and CIDOP-seq data generated in this study have been deposited in the public Gene Expression Omnibus under GEO accession code GSE226768. The human reference genome GRCh38.p12 (GCA_000001405.27) used in this study is available from the National Center for Biotechnology Information [https://www.ncbi.nlm.nih.gov/datasets/genome/GCF_000001405.27/], and the HeLa H3K4me3 data used in Supplementary Fig. 3 is available from the ENCODE Portal [https://www.encodeproject.org/files/ENCFF489CIY/]. Source data are provided with this paper.
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