Release of Histone H3K4-reading transcription factors from chromosomes in mitosis is independent of adjacent H3 phosphorylation

Harris, R. J.; Heer, M.; Levasseur, M. D.; Cartwright, T. N.; Weston, B.; Mitchell, J. L.; Coxhead, J. M.; Gaughan, L.; Prendergast, L.; Rico, D.; Higgins, J. M. G.

doi:10.1101/2023.02.28.530230

bioRxiv · 10.1101/2023.02.28.530230

Release of Histone H3K4-reading transcription factors from chromosomes in mitosis is independent of adjacent H3 phosphorylation

Harris, R. J.·Heer, M.·Levasseur, M. D.·Cartwright, T. N.·Weston, B.·Mitchell, J. L.·Coxhead, J. M.·Gaughan, L.·Prendergast, L.·Rico, D.·Higgins, J. M. G.

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Abstract

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 particular 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 recognise 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 H3K4me3 during mitosis. We find that H3K4me3 hinders adjacent H3T3ph deposition in cells, and that the PHD domain of TAF3 can bind H3K4me3 in mitotic chromatin despite the presence of H3T3ph. Unlike in vitro, H3K4 readers are displaced from chromosomes in mitosis in Haspin-depleted cells lacking H3T3ph. H3T3ph is therefore unlikely to be responsible for transcriptional downregulation during cell division.

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Harris, R. J., Heer, M., Levasseur, M. D., Cartwright, T. N., Weston, B., Mitchell, J. L., Coxhead, J. M., Gaughan, L., Prendergast, L., Rico, D., Higgins, J. M. G.. 2023-03-01. Release of Histone H3K4-reading transcription factors from chromosomes in mitosis is independent of adjacent H3 phosphorylation. https://doi.org/10.1101/2023.02.28.530230

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