一周快讯：本周表观文献精选（2018.1.13）

中科院广州生物院裴端卿课题组揭示细胞命运变化中染色质开关规律

Chromatin Accessibility Dynamics during iPSC Reprogramming

Dongwei Li, Jing Liu, Xuejie Yang6, Chunhua Zhou, Jing Guo, Chuman Wu, Yue Qin, LinGuo, Jiangping He, Shenyong Yu, He Liu, Xiaoshan Wang, Fang Wu, Junqi Kuang, AndrewP. Hutchins, Jiekai Chen, Duanqing Pei.

原文链接：

http://www.cell.com/cell-stem-cell/fulltext/S1934-5909(17)30429-0

原文摘要：Cell-fate decisions remain poorly understood at the chromatin level. Here, we map chromatin remodeling dynamics during induction of pluripotent stem cells. ATAC-seq profiling of MEFs expressing Oct4-Sox2-Klf4 (OSK) reveals dynamic changes in chromatin states shifting from open to closed (OC) and closed to open (CO), with an initial burst of OC and an ending surge of CO. The OC loci are largely composed of genes associated with a somatic fate, while the CO loci are associated with pluripotency. Factors/conditions known to impede reprogramming prevent OSK-driven OC and skew OC-CO dynamics. While the CO loci are enriched for OSK motifs, the OC loci are not, suggesting alternative mechanisms for chromatin closing. Sap30, a Sin3A corepressor complex component, is required for the OC shift and facilitates reduced H3K27ac deposition at OC loci. These results reveal a chromatin accessibility logic during reprogramming that may apply to other cell-fate decisions.

中科院生物物理所朱冰组与北生所袭荣文组合作揭示H3K36me2甲基转移酶Ash1的关键调节因子

Mrg15 stimulates Ash1 H3K36 methyltransferase activity and facilitates Ash1 Trithorax group protein function in Drosophila

Chang Huang,Fu Yang, Zhuqiang Zhang, Jing Zhang, Gaihong Cai, Lin Li, YongZheng, She Chen, Rongwen Xi & Bing Zhu

原文链接 ：

https://www.nature.com/articles/s41467-017-01897-3

原文摘要：Ash1 is a Trithorax group protein that possesses H3K36-specific histone methyltransferase activity, which antagonizes Polycomb silencing. Here we report the identification of two Ash1 complex subunits, Mrg15 and Nurf55. In vitro, Mrg15 stimulates the enzymatic activity of Ash1. In vivo, Mrg15 is recruited by Ash1 to their common targets, and Mrg15 reinforces Ash1 chromatin association and facilitates the proper deposition of H3K36me2. To dissect the functional role of Mrg15 in the context of the Ash1 complex, we identify an Ash1 point mutation (Ash1-R1288A) that displays a greatly attenuated interaction with Mrg15. Knock-in flies bearing this mutation display multiple homeotic transformation phenotypes, and these phenotypes are partially rescued by overexpressing the Mrg15-Nurf55 fusion protein, which stabilizes the association of Mrg15 with Ash1. In summary, Mrg15 is a subunit of the Ash1 complex, a stimulator of Ash1 enzymatic activity and a critical regulator of the TrxG protein function of Ash1 in Drosophila.

瑞典科学家揭示了化学相互作用原则

A Map of Protein-Metabolite Interactions Reveals Principles of Chemical Communication

Ilaria Piazza, Karl Kochanowski, Valentina Cappelletti, Tobias Fuhrer, Elad Noor, UweSauer,Paola Picotti

原文链接 ：

http://www.cell.com/cell/fulltext/S0092-8674(17)31448-4

原文摘要：Metabolite-protein interactions control a variety of cellular processes, thereby playing a major role in maintaining cellular homeostasis. Metabolites comprise the largest fraction of molecules in cells, but our knowledge of the metabolite-protein interactome lags behind our understanding of protein-protein or protein-DNA interactomes. Here, we present a chemoproteomic workflow for the systematic identification of metabolite-protein interactions directly in their native environment. The approach identified a network of known and novel interactions and binding sites in Escherichia coli , and we demonstrated the functional relevance of a number of newly identified interactions. Our data enabled identification of new enzyme-substrate relationships and cases of metabolite-induced remodeling of protein complexes. Our metabolite-protein interactome consists of 1,678 interactions and 7,345 putative binding sites. Our data reveal functional and structural principles of chemical communication, shed light on the prevalence and mechanisms of enzyme promiscuity, and enable extraction of quantitative parameters of metabolite binding on a proteome-wide scale.