The histone H2A N‐terminal tail regulates H2B monoubiquitylation and H3 K4 methylation via a novel trans tail pathway

Abstract

The roles of the histone H3 and H4 N‐terminal tails in regulating chromatin structure and gene transcription have been extensively studied. However, very little is known about the functions of the H2A N‐terminal tail in transcription regulation. We analyzed multiple histone modifications associated with active transcription in the absence of the histone H2A tail. Our results reveal a novel trans‐tail regulation between the H2A tail and H2BK123 monoubiquitylation (H2BK123ub). Deletion of the H2A tail, or as little as four amino acids (a.a. 16–20), leads to a significant decrease in H2BK123ub, followed by a global reduction in H3K4 methylation by COMPASS. COMPASS complex purified from a H2A tail deletion strain lacks the Cps35 subunit, similar to the complex purified from a RAD6 deletion mutant. Rad6, which is responsible for ubiquitylating H2B K123, is still capable of being targeted to genes in the absence of the H2A tail, suggesting a type of post‐recruitment regulation. Deletion of the H2A tail causes a lag in the induction time of the GAL1 gene compared to wild type. Additionally, we show that deleting the Ubp8 and Ubp10 deubiquitylases not only restores the normal rate of induction of GAL1, but also restores H2BK123ub and H3K4me3 levels within the cell. Our analysis uncovers a role for the H2A tail in regulating transcription by maintaining a proper level of H2BK123 ubiquitylation and H3K4 methylation.This research was supported by funds from National Institutes of Health (GM58672) to J.C.R.