Jbara Muhammad, Guttmann-Raviv Noga, Maity Suman Kumar, Ayoub Nabieh, Brik Ashraf
Schulich Faculty of Chemistry, Technion-Israel Institute of Technology, Haifa 3200008, Israel; Department of Biology, Technion-Israel Institute of Technology, Haifa 3200003, Israel.
Department of Biology, Technion-Israel Institute of Technology, Haifa 3200003, Israel.
Bioorg Med Chem. 2017 Sep 15;25(18):4966-4970. doi: 10.1016/j.bmc.2017.04.015. Epub 2017 Apr 12.
Histone H3 methylation plays an important role in regulating gene expression. In histones in general, this mark is dynamically regulated via various demethylases, which found to control cell fate decisions as well as linked to several diseases, including neurological and cancer. Despite major progress in studying methylation mark at various positions in H3 histone proteins, less is known about the regulation of methylated H3 at Lys79. Methylation at this site is known to have direct cross-talk with monoubiquitination of histone H2B at positions Lys120 and 34, as well as with acetylated H3 at Lys9. Herein we applied convergent total chemical protein synthesis to prepare trimethylated H3 at Lys79 to perform initial studies related to the regulation of this mark. Our study enabled us to identify KDM4D lysine demethylase as a potential regulator for trimethylated H3 at Lys79.
组蛋白H3甲基化在调节基因表达中起重要作用。一般来说，在组蛋白中，这种标记通过各种去甲基化酶进行动态调节，这些去甲基化酶被发现可控制细胞命运决定，并与包括神经疾病和癌症在内的多种疾病有关。尽管在研究H3组蛋白不同位置的甲基化标记方面取得了重大进展，但对于赖氨酸79处甲基化H3的调节了解较少。已知该位点的甲基化与组蛋白H2B赖氨酸120和34位的单泛素化以及赖氨酸9处的乙酰化H3有直接相互作用。在此，我们应用汇聚式全化学蛋白质合成方法制备赖氨酸79处三甲基化的H3，以开展与该标记调节相关的初步研究。我们的研究使我们能够确定KDM4D赖氨酸去甲基化酶是赖氨酸79处三甲基化H3的潜在调节因子。
