Activation of gene expression by histone deubiquitinase OTLD1

Abstract

ABSTRACTOne of the main mechanisms of epigenetic control is post translational modification of histones, and one of the relatively less characterized, yet functionally important histone modifications is monoubiquitylation, which is reversed by histone deubiquitinases. In Arabidopsis, only two of such enzymes are known to date. One of them, OTLD1, deubiquitylates histone 2B and functions as a transcriptional repressor. But, could the same deubiquitinase act both as a repressor and an activator? Here, we addressed this question. Using gain-of-function and loss-of-function Arabidopsis alleles, we showed that OTLD1 can promote expression of a target gene. This transcriptional activation activity of OTLD1 involves occupation of the target chromatin by this enzyme, deubiquitination of monoubiquitylated H2B within the occupied regions, and formation of the euchromatic histone acetylation and methylation marks. Thus, OTLD1 can play a dual role in transcriptional repression and activation of its target genes. In these reactions, H2B ubiquitylation acts as both a repressive and an active mark whereas OTLD1 association with and deubiquitylation of the target chromatin may represent the key juncture between two opposing effects of this enzyme on gene expression.