Crotonyl-Histone H3 (Lys18) (E8D9M) Rabbit mAb

The nucleosome, made up of four core histone proteins (H2A, H2B, H3, and H4), is the primary building block of chromatin. Originally thought to function as a static scaffold for DNA packaging, histones have now been shown to be dynamic proteins, undergoing multiple types of post-translational modifications, including acetylation, phosphorylation, methylation, and ubiquitination (1,2). Histone crotonylation is an evolutionarily conserved process that is correlated with the amount of available cellular crotonyl-CoA. The addition of crotonyl groups is facilitated by CBP, p300, as well as the conserved MOF enzyme (3,4). Crotonylation is generally found at actively transcribed gene promoters, and has been uniquely implicated in male germ cell gene expression (3,5). While structurally similar to acetyl groups, crotonyl groups are not read by bromodomains, and are instead read by YEATS and DPF domains (6-8). Key chromatin regulators have been shown to have great affinity to crotonyl marks, including MYST3 and DPF2, a member of the BAF chromatin remodeling complex (9). Much like acetylation, crotonylation is dynamically regulated, and class I deacetylases HDAC1/2/3 have been shown to be capable of decrotonylation (10,11). Furthermore, crotonylation can be negatively regulated by CDYL, which can convert crotonyl-CoA to β-hydroxybutyryl-CoA (12). Crotonylation has been linked to metabolic state, as limited energy sources cause a global reduction in H3K9 acetylation and an increase in H3K9 crotonylation (13). While crotonylation is generally found at active genes, H3K27cr is recognized by GAS41 along with the SIN3A-HDAC1 corepressive complex and is associated with a gene repression program distinct from H3K27 trimethylation (14). 1.Peterson, C.L. and Laniel, M.A. (2004) Curr Biol 14, R546-51. 2.Jaskelioff, M. and Peterson, C.L. (2003) Nat Cell Biol 5, 395-9. 3.Tan, M. et al. (2011) Cell 146, 1016-28. 4.Liu, X. et al. (2017) Cell Discov 3, 17016. 5.Montellier, E. et al. (2012) Bioessays 34, 187-93. 6.Li, Y. et al. (2016) Mol Cell 62, 181-193. 7.Andrews, F.H. et al. (2016) Nat Chem Biol 12, 396-8. 8.Zhao, D. et al. (2016) Cell Res 26, 629-32. 9.Xiong, X. et al. (2016) Nat Chem Biol 12, 1111-1118. 10.Wei, W. et al. (2017) Cell Res 27, 898-915. 11.Kelly, R.D.W. et al. (2018) Sci Rep 8, 14690. 12.Liu, S. et al. (2017) Mol Cell 67, 853-866.e5. 13.Gowans, G.J. et al. (2019) Mol Cell 76, 909-921.e3. 14.Liu, N. et al. (2023) Mol Cell 83, 2206-2221.e11.