Abstract
Chromatin modifiers and histone modifications are components of a chromatin-signaling network involved in transcription and its regulation. The interactions between chromatin modifiers and histone modifications are often unknown, are based on the analysis of few genes or are studied in vitro. Here, we apply computational methods to recover interactions between chromatin modifiers and histone modifications from genome-wide ChIP-Seq data. These interactions provide a high-confidence backbone of the chromatin-signaling network. Many recovered interactions have literature support; others provide hypotheses about yet unknown interactions. We experimentally verified two of these predicted interactions, leading to a link between H4K20me1 and members of the Polycomb Repressive Complexes 1 and 2. Our results suggest that our computationally derived interactions are likely to lead to novel biological insights required to establish the connectivity of the chromatin-signaling network involved in transcription and its regulation.
Highlights
Transcription and its regulation are facilitated by a complex interplay between various molecular players, such as transcription factors, chromatin modifiers (CMs), histone modifications (HMs) and RNA polymerase II (Pol II)
HMs and CMs, are components of the chromatinsignaling network involved in transcription and its regulation, both should contain information about gene expression
The good predictive performance confirms that both HMs and CMs contain extensive information about gene expression
Summary
Transcription and its regulation are facilitated by a complex interplay between various molecular players, such as transcription factors, chromatin modifiers (CMs), histone modifications (HMs) and RNA polymerase II (Pol II). Together these components form a chromatin-signaling network [1] whose signaling activity affects the transcriptional and the chromatin state of a particular genomic region. It is not surprising that the presence of certain HMs at the promoter or the gene body coincides with the transcriptional status of the corresponding gene [2,3] This close link is further substantiated by the finding that there is even a quantitative relationship between HM levels and the steady-state level of mRNAs [4,5,6]. Because histones are firmly bound to DNA, HMs may restrict the signaling activity to certain genomic features, such as enhancers and promoters
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