Identification of 67 Histone Marks and Histone Lysine Crotonylation as a New Type of Histone Modification

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. [Display omitted] ► Identification of 67 novel histone marks including 28 lysine crotonylation sites ► Verification of Kcr as a novel histone mark ► Kcr is a robust indicator of active cellular genes ► Kcr is likely an important histone mark for male germ cell differentiation This resource identifies new additions to the histone code. Among them, histone crotonlylation emerges as a mark enriched at testis-specific genes that escape sex chromosome inactivation in germ cells.