Global profiling of regulatory elements in the histone benzoylation pathway

• Published in: Nature communications 2022-03, Vol.13 (1), p.1369-1369, Article 1369
• Main Authors: Wang, Duo, Yan, Fuxiang, Wu, Ping, Ge, Kexue, Li, Muchun, Li, Tingting, Gao, Ying, Peng, Chao, Chen, Yong
• Format: Article
• Language: English
• Subjects: 14/1; 38/70; 631/337/100/2285; 631/45/475; 631/45/607; 631/535/1266; 82/16; 82/29; 82/83; Acetyltransferase; Benzoylation; Catalysis; Crystal structure; Gluconeogenesis; Glycolysis; Histone Acetyltransferases - metabolism; Histone deacetylase; Histones; Histones - metabolism; Humanities and Social Sciences; Lysine; Lysine - metabolism; multidisciplinary; NAD; Post-translation; Protein Processing, Post-Translational; Proteins; Proteomes; Proteomics; Regulatory sequences; RNA processing; rRNA; Saccharomyces cerevisiae; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - metabolism; Science; Science (multidisciplinary); Sirtuin 2 - metabolism; Transcription; Yeast; Yeasts
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-29057-2

Lysine benzoylation (Kbz) is a recently discovered post-translational modification associated with active transcription. However, the proteins for maintaining and interpreting Kbz and the physiological roles of Kbz remain elusive. Here, we systematically characterize writer, eraser, and reader proteins of histone Kbz in S. cerevisiae using proteomic, biochemical, and structural approaches. Our study identifies 27 Kbz sites on yeast histones that can be regulated by cellular metabolic states. The Spt-Ada-Gcn5 acetyltransferase (SAGA) complex and NAD + -dependent histone deacetylase Hst2 could function as the writer and eraser of histone Kbz, respectively. Crystal structures of Hst2 complexes reveal the molecular basis for Kbz recognition and catalysis by Hst2. In addition, we demonstrate that a subset of YEATS domains and bromodomains serve as Kbz readers, and structural analyses reveal how YEATS and bromodomains recognize Kbz marks. Moreover, the proteome-wide screening of Kbz-modified proteins identifies 207 Kbz sites on 149 non-histone proteins enriched in ribosome biogenesis, glycolysis/gluconeogenesis, and rRNA processing pathways. Our studies identify regulatory elements for the Kbz pathway and provide a framework for dissecting the biological functions of lysine benzoylation. Lysine benzoylation (Kbz) is a recently discovered histone modification. Here, the authors characterize writers, erasers and readers of histone Kbz in S. cerevisiae and identify non-histone proteins bearing Kbz, laying foundations to dissect the roles of Kbz in diverse cellular processes.