Dynamic Histone Propionylation:Enzymes And Function In Transcription By Metabolic Regulation

Histone lysine propionylation(Kpro)is a novel histone post transcriptional modification,which is dynamically regulated by HPTs(Histone propionyltransferases)and HDPRs(Histone depropionylases).The propionyl group could be provided by propionyl-Co A.Previous studies have demonstrated that CBP/p300 and PCAF/GCN5 have the HPT enzymatic activity,and SIRT1-3 could be the enzyme responsible for histone depropionylation in vitro.However,the HPTs and HDPRs in vivo remain to be identified.And the functions of histone propionylation are still unclear.Firstly,we identified the main celluar enzymes for histone propionylation and depropionylation.Based on the similar structure of propionyl group and acetyl group,we used Immunofluourescence staining assays and Western blot to screen the HATs families(include CBP/p300 family,GCN5 family and MYST family)for HPTs and HDACs families(include HDAC1-11 and SIRT1-7)for HDPRs.Here we demonstrate that CBP/p300,GCN5,MOF and HBO1(co-expressed with Jade1)possess HPT enzymatic activity.And Class I histone deacetylases(HDACs)are the major histone depropionylases.After hepatoma cell line Bel7402 is treated with starvation,we find that histone propionylation level increased,and histone acetylation level decreased,while the other histone modifications don't change significantly.And we also find that the starvation-induced gene transcription are associated with fatty acid oxidation.Type2diabetes(T2D)is a major metabolic disease.We find that histone propionylation level in T2 D increased.And the results suggest that histone propionylation might be associated with T2 D development.This may provide some cures for the clinical treatment of T2D in the future.