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Modeling gene expression using chromatin features in various cellular contexts

DOI: 10.1186/gb-2012-13-9-r53

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Abstract:

We built a novel quantitative model to study the relationship between chromatin features and expression levels. Our study not only confirms that the general relationships found in previous studies hold across various cell lines, but also makes new suggestions about the relationship between chromatin features and gene expression levels. We found that expression status and expression levels can be predicted by different groups of chromatin features, both with high accuracy. We also found that expression levels measured by CAGE are better predicted than by RNA-PET or RNA-Seq, and different categories of chromatin features are the most predictive of expression for different RNA measurement methods. Additionally, PolyA+ RNA is overall more predictable than PolyA- RNA among different cell compartments, and PolyA+ cytosolic RNA measured with RNA-Seq is more predictable than PolyA+ nuclear RNA, while the opposite is true for PolyA- RNA.Our study provides new insights into transcriptional regulation by analyzing chromatin features in different cellular contexts.Gene expression refers to the process of producing a specific amount of gene product in a spatiotemporal manner. It is highly regulated in many steps, including transcriptional regulation, splicing, end modification, export, and degradation. Transcriptional regulation can occur on both genetic and epigenetic levels. Here, we define genetic regulation as a direct or indirect interaction between a gene and a transcription factor, and epigenetic regulation as altering DNA accessibility to transcription factors by chemical modification of chromatin. The basic unit of chromatin is structured like beads on a string, where the string is DNA and each bead is a DNA-protein complex called a nucleosome. Nucleosomes are an octameric complex of histone proteins composed of two copies of four core histones (H2A, H2B, H3 and H4) with roughly 147 bp of DNA wrapped around each octamer. Several post-translational modifications, such as

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