Histone modifications form a cell-type-specific chromosomal bar code that persists through the cell cycle

Abstract Chromatin configuration influences gene expression in eukaryotes at multiple levels, from individual nucleosomes to chromatin domains several Mb long. Post-translational modifications (PTM) of core histones seem to be involved in chromatin structural transitions, but how remains unclear. To...

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Autores principales:	John A. Halsall, Simon Andrews, Felix Krueger, Charlotte E. Rutledge, Gabriella Ficz, Wolf Reik, Bryan M. Turner
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/638296035c4644d5b4cc65f25c7d7cda
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spelling	oai:doaj.org-article:638296035c4644d5b4cc65f25c7d7cda2021-12-02T10:44:09ZHistone modifications form a cell-type-specific chromosomal bar code that persists through the cell cycle10.1038/s41598-021-82539-z2045-2322https://doaj.org/article/638296035c4644d5b4cc65f25c7d7cda2021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82539-zhttps://doaj.org/toc/2045-2322Abstract Chromatin configuration influences gene expression in eukaryotes at multiple levels, from individual nucleosomes to chromatin domains several Mb long. Post-translational modifications (PTM) of core histones seem to be involved in chromatin structural transitions, but how remains unclear. To explore this, we used ChIP-seq and two cell types, HeLa and lymphoblastoid (LCL), to define how changes in chromatin packaging through the cell cycle influence the distributions of three transcription-associated histone modifications, H3K9ac, H3K4me3 and H3K27me3. We show that chromosome regions (bands) of 10–50 Mb, detectable by immunofluorescence microscopy of metaphase (M) chromosomes, are also present in G1 and G2. They comprise 1–5 Mb sub-bands that differ between HeLa and LCL but remain consistent through the cell cycle. The same sub-bands are defined by H3K9ac and H3K4me3, while H3K27me3 spreads more widely. We found little change between cell cycle phases, whether compared by 5 Kb rolling windows or when analysis was restricted to functional elements such as transcription start sites and topologically associating domains. Only a small number of genes showed cell-cycle related changes: at genes encoding proteins involved in mitosis, H3K9 became highly acetylated in G2M, possibly because of ongoing transcription. In conclusion, modified histone isoforms H3K9ac, H3K4me3 and H3K27me3 exhibit a characteristic genomic distribution at resolutions of 1 Mb and below that differs between HeLa and lymphoblastoid cells but remains remarkably consistent through the cell cycle. We suggest that this cell-type-specific chromosomal bar-code is part of a homeostatic mechanism by which cells retain their characteristic gene expression patterns, and hence their identity, through multiple mitoses.John A. HalsallSimon AndrewsFelix KruegerCharlotte E. RutledgeGabriella FiczWolf ReikBryan M. TurnerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-19 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q John A. Halsall Simon Andrews Felix Krueger Charlotte E. Rutledge Gabriella Ficz Wolf Reik Bryan M. Turner Histone modifications form a cell-type-specific chromosomal bar code that persists through the cell cycle
description	Abstract Chromatin configuration influences gene expression in eukaryotes at multiple levels, from individual nucleosomes to chromatin domains several Mb long. Post-translational modifications (PTM) of core histones seem to be involved in chromatin structural transitions, but how remains unclear. To explore this, we used ChIP-seq and two cell types, HeLa and lymphoblastoid (LCL), to define how changes in chromatin packaging through the cell cycle influence the distributions of three transcription-associated histone modifications, H3K9ac, H3K4me3 and H3K27me3. We show that chromosome regions (bands) of 10–50 Mb, detectable by immunofluorescence microscopy of metaphase (M) chromosomes, are also present in G1 and G2. They comprise 1–5 Mb sub-bands that differ between HeLa and LCL but remain consistent through the cell cycle. The same sub-bands are defined by H3K9ac and H3K4me3, while H3K27me3 spreads more widely. We found little change between cell cycle phases, whether compared by 5 Kb rolling windows or when analysis was restricted to functional elements such as transcription start sites and topologically associating domains. Only a small number of genes showed cell-cycle related changes: at genes encoding proteins involved in mitosis, H3K9 became highly acetylated in G2M, possibly because of ongoing transcription. In conclusion, modified histone isoforms H3K9ac, H3K4me3 and H3K27me3 exhibit a characteristic genomic distribution at resolutions of 1 Mb and below that differs between HeLa and lymphoblastoid cells but remains remarkably consistent through the cell cycle. We suggest that this cell-type-specific chromosomal bar-code is part of a homeostatic mechanism by which cells retain their characteristic gene expression patterns, and hence their identity, through multiple mitoses.
format	article
author	John A. Halsall Simon Andrews Felix Krueger Charlotte E. Rutledge Gabriella Ficz Wolf Reik Bryan M. Turner
author_facet	John A. Halsall Simon Andrews Felix Krueger Charlotte E. Rutledge Gabriella Ficz Wolf Reik Bryan M. Turner
author_sort	John A. Halsall
title	Histone modifications form a cell-type-specific chromosomal bar code that persists through the cell cycle
title_short	Histone modifications form a cell-type-specific chromosomal bar code that persists through the cell cycle
title_full	Histone modifications form a cell-type-specific chromosomal bar code that persists through the cell cycle
title_fullStr	Histone modifications form a cell-type-specific chromosomal bar code that persists through the cell cycle
title_full_unstemmed	Histone modifications form a cell-type-specific chromosomal bar code that persists through the cell cycle
title_sort	histone modifications form a cell-type-specific chromosomal bar code that persists through the cell cycle
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/638296035c4644d5b4cc65f25c7d7cda
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Histone modifications form a cell-type-specific chromosomal bar code that persists through the cell cycle

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