Confident gene activity prediction based on single histone modification H2BK5ac in human cell lines

Abstract

BackgroundThe histones in the core of nucleosomes may be subject to covalent post-transcriptional modifications. These modifications are thought to correlate with and possibly affect various genomic functions, including transcription. Each modification may alone or in combination with other modifications influence or be influenced by transcription. We aimed to identify correlations between single modifications or combinations of modifications at specific nucleosome sized gene regions with transcription activity based on global histone modification and transcription data of human CD4+ T cells and three other human cell lines. Transcription activity was defined in a binary fashion as either on or off. The analysis was done using the Classification and Regression Tree (CART) data mining protocol, and the Multifactorial Dimensionality Reduction (MDR) method was performed to confirm the CART results. These powerful methods have not previously been used for analysis of histone modification data.ResultsWe showed that analysis of the single histone modification H2BK5ac at only four gene regions correctly predicted transcription activity status of over 75% of genes in CD4+ T-cells. The H2BK5ac modification status also had high power for prediction of gene transcription activity in the three other cell lines studied. The informative gene regions with the H2BK5ac modification were all positioned proximal to transcription initiation sites. The CART and MDR methods were appropriate tools for the analysis performed. In the study, we also developed a non-arbitrary protocol for binary classification of genes as transcriptionally active or inactive.ConclusionsThe importance of H2BK5ac modification with regards to transcription control has not previously been emphasized. Analysis of this single modification at only four nucleosome sized gene regions, all of which are at or proximal to transcription initiation, has high power for prediction of gene transcription activity.Electronic supplementary materialThe online version of this article (doi:10.1186/s12859-016-1418-6) contains supplementary material, which is available to authorized users.

Identification of histone acetylation in a murine model of allergic asthma by proteomic analysis

“…Studies elucidating the roles of histone H2B in asthma are limited. Despite the correlation of H2BK5ac and asthma has not been demonstrated, recent data suggested that EMT is regulated by H2BK5ac, 32,33 thus we speculated that H2BK5ac participated in the pathogenesis of asthma via regulating EMT. Besides, H2BK20ac and H2BK120ac have been proven a strong correlation with DNA methylation, 34 which hinted that they may regulate gene expression to affect disease development.…”

Comprehensive Transcriptomic Analysis of Novel Class I HDAC Proteolysis Targeting Chimeras (PROTACs)

“…To test the ability of PROTACs to penetrate cells and inhibit class I HDACs, we measured lysine acetylation levels in histone tails. We examined two independent sites of acetylation, Lys56 on histone H3 (H3K56ac), a known HDAC1/2 substrate, 34 and Lys5 on histone H2B (H2BK5ac), a mark of active transcription, 35 by quantitative Western blotting ( Figure 2 B). Treatment of cells with CI-994 produced robust 20- and 15-fold increases in H3K56ac and H2BK5ac levels, respectively, compared to controls.…”

Repression of the PRELP gene is relieved by histone deacetylase inhibitors through acetylation of histone H2B lysine 5 in bladder cancer

“…Recent data suggest that H2BK5ac is a reliable predictor of gene expression [ 51 ] and an important modifier in the orchestration of EMT programs. Mechanistically, MAP3K4-regulated chromatin modifiers CBP and HDAC6 each regulate thousands of genes during EMT by controlling promoter acetylation of H2BK5 [ 52 , 53 ].…”