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.
Highlights
The histones in the core of nucleosomes may be subject to covalent post-transcriptional modifications
Our findings suggest that data on two modifications at four nucleosome sized gene regions provide maximum power for prediction of gene activity in Cluster of differentiation 4 (CD4)+ T- cells, and that knowledge of presence or absence of the single modification H2BK5ac at four gene regions reveals almost the same amount of information
Frequency of various histone modifications at transcription initiation and termination sites of genes with different transcription levels The distribution of frequencies of various histone modifications at the transcription start site (TSS) (Transcription Start Site) and TTS (Transcription Termination site) in the 19 groups of genes grouped on the basis of log2 levels of gene transcription value are shown in Fig. 1a, b
Summary
The 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. 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. We aimed to identify the most informative correspondence between pattern of histone modifications and transcription using the Classification and Regression Tree)CART( [19] and the exhaustive Multifactorial Dimensionality Reduction (MDR) methods [20, 21]. In order to classify genes as active or inactive, a protocol for designating a value threshold was developed
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