Lysine succinylation on non-histone chromosomal protein HMG-17 (HMGN2) regulates nucleosomal DNA accessibility by disrupting the HMGN2-nucleosome association

Yihang Jing; Gaofei Tian; Xiaoyu Qin; Zheng Liu; Xiang David Li

doi:10.1039/d1cb00070e

Lysine succinylation on non-histone chromosomal protein HMG-17 (HMGN2) regulates nucleosomal DNA accessibility by disrupting the HMGN2-nucleosome association

RSC Chem Biol. 2021 May 27;2(4):1257-1262. doi: 10.1039/d1cb00070e. eCollection 2021 Aug 5.

Authors

Yihang Jing¹, Gaofei Tian¹, Xiaoyu Qin¹, Zheng Liu¹, Xiang David Li¹

Affiliation

¹ Department of Chemistry, The University of Hong Kong Pokfulam Road Hong Kong China lz0418@hku.hk xiangli@hku.hk.

Abstract

Lysine succinylation (Ksucc) is a novel posttranslational modification that frequently occurs on chromatin proteins including histones and non-histone proteins. Histone Ksucc affects nucleosome dynamics by increasing the DNA unwrapping rate and accessibility. However, very little is known about the regulation and functions of Ksucc located on non-histone chromosomal proteins. Here, we site-specifically installed a succinyl lysine analogue (K_csucc) onto the non-histone chromosomal protein HMG-17 (HMGN2) to mimic the natural succinylated protein. We found that the incorporation of K_csucc into HMGN2 at the K30 site (HMGN2K_c30succ), which is located within the nucleosome-binding domain (NBD), leads to significantly decreased HMGN2 binding to the mononucleosome. HMGN2K_c30succ also increased the nucleosomal DNA accessibility by promoting nucleosomal DNA unwrapping in the entry/exit region. This study reveals a novel mechanism of non-histone protein succinylation on altering chromatin recruitment, which can further affect nucleosome and chromatin dynamics.