Histone Lysine Crotonylation( Image by Dr. ZHAO Yingming)

Histone post-translational modifications (PTMs) play a crucial regulatory role in diverse biological processes, such as cell differentiation and organismal development, and that aberrant modification of histones contributes to a variety of diseases, such as cancer, neurodegenerative diseases. There are around 95 known histone marks that have been discovered in the past several decades.

An international team led by Professor ZHAO Yingming  at Ben May Department for Cancer Research, University of Chicago, together with the scientists from Shanghai Institute of Materia Medica, Chinese Academy of Sciences (SIMM), University of California, San Diego (UCSD), Université Joseph Fourier, and Stanford University, discovered a novel type of histone mark- lysine crotonylation.

By using an integrated, mass spectrometry-based proteomics approach, they identified 130 PTM sites on human histones, including 67 novel histone marks. This research has not only increased the number of known histone modifications by 70%, but also identified one new type of histone mark, lysine crotonylation (Kcr), a novel and evolutionarily-conserved histone PTM. The unique structure and genomic localization of Kcr suggest that it is mechanistically and functionally different from a well known histone mark-lysine acetylation.

They further showed that histone lysine crotonylation marks either active promoters or potential enhancers, and is a specific mark of active sex chromosome-linked genes in post-meiotic male germ cells. This study therefore reveals an important novel mechanism of epigenetics and the novel histone marks provide a stepping stone for the future studies of these pathways in cellular physiology and diseases.

This work was recently published online in the November 16 issue of Cell. Shortly after publication, this research was highlighted by Nature Reviews Genetics and will be published in its November issue.

The senior author of this paper, Dr. ZHAO Yingming, was recruited recently by SIMM as an adjunct faculty member, who will co-direct its newly established Chemical Proteomics Center (CPC) in SIMM. The establishment of CPC follows SIMM’s new strategy for the enhancement of the quality of basic research and efficiency for drug development in “the twelfth five-year-plan”, through the collaboration with Dr. ZHAO Yingming . The CPC, founded in July, 2011, aims to develop mass spectrometry-based proteomics technologies for comprehensive analysis of protein targets of PTM regulatory enzymes and biomarker discovery for personalized medicine.

Article Link：http://www.cell.com/abstract/S0092-8674(11)00891-9；