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  • Identification of lysine isobutyrylation as a new histone modification mark.

Identification of lysine isobutyrylation as a new histone modification mark.

Nucleic acids research (2020-12-15)
Zhesi Zhu, Zhen Han, Levon Halabelian, Xiangkun Yang, Jun Ding, Nawei Zhang, Liza Ngo, Jiabao Song, Hong Zeng, Maomao He, Yingming Zhao, Cheryl H Arrowsmith, Minkui Luo, Michael G Bartlett, Y George Zheng
ABSTRACT

Short-chain acylations 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 in vitro, especially p300 and HAT1. Transfection and western blot experiments showed that p300 regulated histone isobutyrylation levels in the cell. 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. Together, our findings identify Kibu as a novel chemical modification mark in histones and suggest its extensive role in regulating epigenetics and cellular physiology.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Isobutyric-d7 acid, 98 atom % D, 99% (CP)
Pricing and availability is not currently available.
Sigma-Aldrich
Acetyl coenzyme A lithium salt, ≥93% (HPLC)
Pricing and availability is not currently available.
Sigma-Aldrich
L-Valine, reagent grade, ≥98% (HPLC)
Pricing and availability is not currently available.
Sigma-Aldrich
Butyryl coenzyme A lithium salt hydrate, ≥90%
Pricing and availability is not currently available.