Identification of 67 Histone Marks and Histone Lysine Crotonylation as a New Type of Histone Modification
Open accessAbstract
We report the identification of 67 previously undescribed histone modifications, increasing the current number of known histone marks by about 70%. We further investigated one of the marks, lysine crotonylation (Kcr), confirming that it represents an evolutionarily-conserved histone posttranslational modification. The unique structure and genomic localization of histone Kcr suggest that it is mechanistically and functionally different from histone lysine acetylation (Kac). Specifically, in both human somatic and mouse male germ cell genomes, histone Kcr marks either active promoters or potential enhancers. In male germinal cells immediately following meiosis, Kcr is enriched on sex chromosomes and specifically marks testis-specific genes, including a significant proportion of X-linked genes that escape sex chromosome inactivation in haploid cells. These results therefore dramatically extend the repertoire of histone PTM sites and designate Kcr as a specific mark of active sex chromosome-linked genes in postmeiotic male germ cells.
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Histone crotonylation occurs at promoters or enhancers of actively transcribed genes and plays a role in spermatogenesis.
“Histone crotonylation was previously shown to occur at the promoters or enhancers of gens that are actively transcribed, and play a role in spermatogenesis.111,179”
From Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential (2023) · cites this paper as [179]
The Discussion reports that histone Kcr marks enhancers and transcription start sites of active genes in human somatic and mouse male germ cells. It also observes Kcr during spermatogenesis, but describes its proposed contribution to histone replacement as likely rather than established; the claim overstates that functional role. (LLM, conf=0.84)
Experimental — accuracy not yet measuredHistone lysine crotonylation is associated with active chromatin and overlaps with known sites of lysine acetylation.
“A number of functional studies have concentrated on histone lysine-crotonylation (Lys-cr) which is associated with active chromatin and overlaps with known sites of lysine-acetylation (Lys-ac)3,9.”
From Histone deacetylase (HDAC) 1 and 2 complexes regulate both histone acetylation and crotonylation in vivo (2018) · cites this paper as [3]
Previous studies failed to detect significant decrotonylase activity for HDAC1/2.
“Previous studies failed to detect significant decrotonylase activity for HDAC1/23,18 and this may be because they were using recombinant enzymes generated in isolation.”
From Histone deacetylase (HDAC) 1 and 2 complexes regulate both histone acetylation and crotonylation in vivo (2018) · cites this paper as [3]
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- Authors
- Tan, M., Luo, H., Lee, S., Jin, F., Yang, J. S., Montellier, E., Buchou, T., Cheng, Z., Rousseaux, S., Rajagopal, N., Lu, Z., Ye, Z., Zhu, Q., Wysocka, J., Ye, Y., Khochbin, S., Ren, B., & Zhao, Y.
- Affiliations
- University of Chicago (US)
- University of California San Diego (US)
- Inserm (FR)
- Chinese Academy of Sciences (CN)
- Stanford Medicine (US)
- Corresponding author
- Zhao, Yingming
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2011-09
- Volume
- 146
- Issue
- 6
- Pages
- 1016-1028
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC3176443
- OpenAlex
- W2115862579
- Cited by
- 1,902
- References
- 61
- Citations by year
- 2026: 114 · 2025: 144 · 2024: 144 · 2023: 140 · 2022: 127 · 2021: 143 · 2020: 119 · 2019: 108 · 2018: 121 · 2017: 111 · 2016: 138 · 2015: 133 · 2014: 136 · 2013: 110 · 2012: 104
- FWCI
- 46.19
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- Funders
- Agence Nationale de la Recherche
- Institut National Du Cancer
- National Institutes of Health
- Direction de l’hospitalisation et de l’offre de Soins
- National Cancer Institute (R01CA126832)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK082664)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer-related gene regulation
- Keywords
- histone modifications, lysine acetylation, male germ cells, sex chromosome inactivation, X-linked genes, testis-specific genes, enhancers, promoter, meiosis, sex chromosomes
- MeSH terms
- Animals, Gene Expression Regulation, HeLa Cells, Histones, Humans, Lysine, Male, Meiosis, Protein Processing, Post-Translational, Testis, Histone Code, Mice
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