H3K18 lactylation marks tissue-specific active enhancers

Eva Galle; Chee-Wai Wong; Adhideb Ghosh; Thibaut Desgeorges; Kate Melrose; Laura C Hinte; Daniel Castellano-Castillo; Magdalena Engl; Joao Agostinho de Sousa; Francisco Javier Ruiz-Ojeda; Katrien De Bock; Jonatan R Ruiz; Ferdinand von Meyenn

doi:10.1186/s13059-022-02775-y

H3K18 lactylation marks tissue-specific active enhancers

Eva Galle, Chee-Wai Wong, Adhideb Ghosh, Thibaut Desgeorges, Kate Melrose, Laura C Hinte, Daniel Castellano-Castillo, Magdalena Engl, Joao Agostinho de Sousa, Francisco Javier Ruiz-Ojeda, Katrien De Bock, Jonatan R Ruiz, Ferdinand von Meyenn

Research output: Contribution to journal › Article › peer-review

68 Citations (Scopus)

Abstract

BACKGROUND: Histone lactylation has been recently described as a novel histone post-translational modification linking cellular metabolism to epigenetic regulation.

RESULTS: Given the expected relevance of this modification and current limited knowledge of its function, we generate genome-wide datasets of H3K18la distribution in various in vitro and in vivo samples, including mouse embryonic stem cells, macrophages, adipocytes, and mouse and human skeletal muscle. We compare them to profiles of well-established histone modifications and gene expression patterns. Supervised and unsupervised bioinformatics analysis shows that global H3K18la distribution resembles H3K27ac, although we also find notable differences. H3K18la marks active CpG island-containing promoters of highly expressed genes across most tissues assessed, including many housekeeping genes, and positively correlates with H3K27ac and H3K4me3 as well as with gene expression. In addition, H3K18la is enriched at active enhancers that lie in proximity to genes that are functionally important for the respective tissue.

CONCLUSIONS: Overall, our data suggests that H3K18la is not only a marker for active promoters, but also a mark of tissue specific active enhancers.

Original language	English
Article number	207
Number of pages	28
Journal	Genome Biology
Volume	23
DOIs	https://doi.org/10.1186/s13059-022-02775-y
Publication status	Published - 3 Oct 2022
Externally published	Yes

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title = "H3K18 lactylation marks tissue-specific active enhancers",

abstract = "BACKGROUND: Histone lactylation has been recently described as a novel histone post-translational modification linking cellular metabolism to epigenetic regulation.RESULTS: Given the expected relevance of this modification and current limited knowledge of its function, we generate genome-wide datasets of H3K18la distribution in various in vitro and in vivo samples, including mouse embryonic stem cells, macrophages, adipocytes, and mouse and human skeletal muscle. We compare them to profiles of well-established histone modifications and gene expression patterns. Supervised and unsupervised bioinformatics analysis shows that global H3K18la distribution resembles H3K27ac, although we also find notable differences. H3K18la marks active CpG island-containing promoters of highly expressed genes across most tissues assessed, including many housekeeping genes, and positively correlates with H3K27ac and H3K4me3 as well as with gene expression. In addition, H3K18la is enriched at active enhancers that lie in proximity to genes that are functionally important for the respective tissue.CONCLUSIONS: Overall, our data suggests that H3K18la is not only a marker for active promoters, but also a mark of tissue specific active enhancers.",

keywords = "Animals, Enhancer Elements, Genetic, Epigenesis, Genetic, Histone Code, Histones/metabolism, Humans, Mice, Promoter Regions, Genetic",

author = "Eva Galle and Chee-Wai Wong and Adhideb Ghosh and Thibaut Desgeorges and Kate Melrose and Hinte, {Laura C} and Daniel Castellano-Castillo and Magdalena Engl and {de Sousa}, {Joao Agostinho} and Ruiz-Ojeda, {Francisco Javier} and {De Bock}, Katrien and Ruiz, {Jonatan R} and {von Meyenn}, Ferdinand",

note = "{\textcopyright} 2022. The Author(s).",

year = "2022",

month = oct,

day = "3",

doi = "10.1186/s13059-022-02775-y",

language = "English",

volume = "23",

journal = "Genome Biology",

issn = "1474-7596",

publisher = "BioMed Central",

}

TY - JOUR

T1 - H3K18 lactylation marks tissue-specific active enhancers

AU - Galle, Eva

AU - Wong, Chee-Wai

AU - Ghosh, Adhideb

AU - Desgeorges, Thibaut

AU - Melrose, Kate

AU - Hinte, Laura C

AU - Castellano-Castillo, Daniel

AU - Engl, Magdalena

AU - de Sousa, Joao Agostinho

AU - Ruiz-Ojeda, Francisco Javier

AU - De Bock, Katrien

AU - Ruiz, Jonatan R

AU - von Meyenn, Ferdinand

PY - 2022/10/3

Y1 - 2022/10/3

N2 - BACKGROUND: Histone lactylation has been recently described as a novel histone post-translational modification linking cellular metabolism to epigenetic regulation.RESULTS: Given the expected relevance of this modification and current limited knowledge of its function, we generate genome-wide datasets of H3K18la distribution in various in vitro and in vivo samples, including mouse embryonic stem cells, macrophages, adipocytes, and mouse and human skeletal muscle. We compare them to profiles of well-established histone modifications and gene expression patterns. Supervised and unsupervised bioinformatics analysis shows that global H3K18la distribution resembles H3K27ac, although we also find notable differences. H3K18la marks active CpG island-containing promoters of highly expressed genes across most tissues assessed, including many housekeeping genes, and positively correlates with H3K27ac and H3K4me3 as well as with gene expression. In addition, H3K18la is enriched at active enhancers that lie in proximity to genes that are functionally important for the respective tissue.CONCLUSIONS: Overall, our data suggests that H3K18la is not only a marker for active promoters, but also a mark of tissue specific active enhancers.

AB - BACKGROUND: Histone lactylation has been recently described as a novel histone post-translational modification linking cellular metabolism to epigenetic regulation.RESULTS: Given the expected relevance of this modification and current limited knowledge of its function, we generate genome-wide datasets of H3K18la distribution in various in vitro and in vivo samples, including mouse embryonic stem cells, macrophages, adipocytes, and mouse and human skeletal muscle. We compare them to profiles of well-established histone modifications and gene expression patterns. Supervised and unsupervised bioinformatics analysis shows that global H3K18la distribution resembles H3K27ac, although we also find notable differences. H3K18la marks active CpG island-containing promoters of highly expressed genes across most tissues assessed, including many housekeeping genes, and positively correlates with H3K27ac and H3K4me3 as well as with gene expression. In addition, H3K18la is enriched at active enhancers that lie in proximity to genes that are functionally important for the respective tissue.CONCLUSIONS: Overall, our data suggests that H3K18la is not only a marker for active promoters, but also a mark of tissue specific active enhancers.

KW - Animals

KW - Enhancer Elements, Genetic

KW - Epigenesis, Genetic

KW - Histone Code

KW - Histones/metabolism

KW - Humans

KW - Mice

KW - Promoter Regions, Genetic

U2 - 10.1186/s13059-022-02775-y

DO - 10.1186/s13059-022-02775-y

M3 - Article

C2 - 36192798

SN - 1474-7596

VL - 23

JO - Genome Biology

JF - Genome Biology

M1 - 207

ER -

H3K18 lactylation marks tissue-specific active enhancers

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