Abstract
Author SummaryHistone methylation regulates gene expression and can have drastic consequences for health if the process is defective. Histone lysine demethylases (KDMs) counteract the activity of methyl-transferases and remove methyl group(s) from histones. KDM3A is a H3K9me2/1 demethylase that performs diverse functions via the regulation of its target genes, which are involved in spermatogenesis, metabolism, and cell differentiation. However, the mechanisms underlying KDM3A regulation of specific genes at specific times are largely unknown. Here we found that a physiological stress—elevated temperature—induces KDM3A phosphorylation in human cells via the MSK1 kinase. This phosphorylated form of KDM3A directly interacts with the transcription factor Stat1, which enables Stat1 to recruit KDM3A to Stat1-binding sequences at the promoters of specific target genes. KDM3A then acts to demethylate H3K9me2/1 at these targets, thereby causing specific gene expression in response to the thermal stress. We conclude that heat shock can affect the expression of many genes in human cells via a novel activation mechanism that is centered around the phosphorylation of KDM3A.
Highlights
Histone modifications, such as methylation and acetylation, regulate RNA synthesis [1,2]
KDM3A is a H3K9me2/1 demethylase that performs diverse functions via the regulation of its target genes, which are involved in spermatogenesis, metabolism, and cell differentiation
This phosphorylated form of KDM3A directly interacts with the transcription factor Stat1, which enables Stat1 to recruit KDM3A to Stat1-binding sequences at the promoters of specific target genes
Summary
Histone modifications, such as methylation and acetylation, regulate RNA synthesis [1,2]. A major breakthrough in this field was the discovery that the methylation of histone tails is a reversible process. This discovery was based on the identification of two classes of histone lysine demethylases (KDMs), namely the FADdependent amine oxidase LSD1 [7] and the Jumonji C (JmjC). KDM3A has been demonstrated to regulate genes that are involved in spermatogenesis [11,12], metabolism [13], and cell differentiation [14]. With such a broad functional diversity, the mechanism by which KDM3A regulates the appropriate gene(s) in vivo at the appropriate time and targets the appropriate element is of great interest
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
