Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.31.270165v1?rss=1 Authors: Zhu, Z., Han, Z., Halabelian, L., Yang, X., Ding, J., Zhang, N., Ngo, L., Song, J., Zeng, H., He, M., Zhao, Y., Arrowsmith, C. H., Luo, M., Bartlett, M. G., Zheng, Y. G. Abstract: Short-chain acylation of lysine residues in eukaryotic proteins are recognized as essential posttranslational chemical modifications (PTMs) that regulate cellular processes from transcription, cell cycle, metabolism, to signal transduction. Lysine butyrylation was initially discovered as a normal straight chain butyrylation (Knbu). Here we report its structural isomer, branched chain butyrylation, i.e. lysine isobutyrylation (Kibu), existing as a new PTM on nuclear histones. Uniquely, isobutyryl-CoA is derived from valine catabolism and branched chain fatty acid oxidation which is distinct from the metabolism of n-butyryl-CoA. Several histone acetyltransferases were found to possess lysine isobutyryltransferase activity, especially p300 and HAT1. We resolved the X-ray crystal structures of HAT1 in complex with isobutyryl-CoA that gleaned an atomic level insight into HAT-catalyzed isobutyrylation. RNA-Seq profiling revealed that isobutyrate greatly affected the expression of genes associated with many pivotal biological pathways. Our findings identify Kibu as a novel chemical modification mark in histones and suggest its extensive role in regulating epigenetics and cellular physiology. Copy rights belong to original authors. Visit the link for more info