Abstract
Transcription factors and histone modifications are vital for the regulation of gene expression. Hence, to estimate the effects of transcription factors binding and histone modifications on gene expression, we construct a statistical model for the genome-wide 15 transcription factors binding data, 10 histone modifications profiles and DNase-I hypersensitivity data in three mammalian. Remarkably, our results show POLR2A and H3K36me3 can highly and consistently predict gene expression in three cell lines. And H3K4me3, H3K27me3 and H3K9ac are more reliable predictors than other histone modifications in human embryonic stem cells. Moreover, genome-wide statistical redundancies exist within and between transcription factors and histone modifications, and these phenomena may be caused by the regulation mechanism. In further study, we find that even though transcription factors and histone modifications offer similar effects on expression levels of genome-wide genes, the effects of transcription factors and histone modifications on predictive abilities are different for genes in independent biological processes.
Highlights
Earlier studies [1,2,3,4] showed transcription factors (TFs) binding and histone modifications (HMs) were critical for gene expression, and the abnormities of TFAS is calculated by the following Eq (TF) association strength (TFAS) is calculated by the following Eq (TF) binding and HMs may affect the cell fate such as differentiation and apoptosis [5]
By analyzing the relations of HMs and TF binding to gene expression, Cheng et al [19] found that HMs or TFs binding in different positions show different predictive abilities, and they suggested HMs and TF binding may be redundant for predicting gene expression levels
We investigate the relative contribution of each TF (HM) or combination of them to gene expression by constructing a support vector regression (SVR) model for the genome-wide 15 TFs binding data, 10 HMs profiles and DNase-I hypersensitivity data in three mammalian, and verify their universality in H1-HESc, Gm12878 and K562 cell lines
Summary
Earlier studies [1,2,3,4] showed transcription factors (TFs) binding and histone modifications (HMs) were critical for gene expression, and the abnormities of TFs binding and HMs may affect the cell fate such as differentiation and apoptosis [5]. TFs can activate or block the initiation of gene transcription by binding to specific DNA sequences in enhancers or promoters [14, 15] or recruiting some chromatinmodifying enzymes to induce the changes of chromatin structure [16]. Karlic et al [20] noticed that different combinations of HMs are needed for predicting the expression levels of genes with different CpG content promoters. We investigate the relative contribution of each TF (HM) or combination of them to gene expression by constructing a support vector regression (SVR) model for the genome-wide 15 TFs binding data, 10 HMs profiles and DNase-I hypersensitivity data in three mammalian, and verify their universality in H1-HESc, Gm12878 and K562 cell lines. We research the effects of TFs and HMs on prediction for genes in independent biological processes
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