Chromatin states accurately classify cell differentiation stages.

PloS One
Jessica L Larson, Guo-Cheng Yuan

Abstract

Gene expression is controlled by the concerted interactions between transcription factors and chromatin regulators. While recent studies have identified global chromatin state changes across cell-types, it remains unclear to what extent these changes are co-regulated during cell-differentiation. Here we present a comprehensive computational analysis by assembling a large dataset containing genome-wide occupancy information of 5 histone modifications in 27 human cell lines (including 24 normal and 3 cancer cell lines) obtained from the public domain, followed by independent analysis at three different representations. We classified the differentiation stage of a cell-type based on its genome-wide pattern of chromatin states, and found that our method was able to identify normal cell lines with nearly 100% accuracy. We then applied our model to classify the cancer cell lines and found that each can be unequivocally classified as differentiated cells. The differences can be in part explained by the differential activities of three regulatory modules associated with embryonic stem cells. We also found that the "hotspot" genes, whose chromatin states change dynamically in accordance to the differentiation stage, are not randomly dis...Continue Reading

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Citations

Apr 11, 2013·Genomics·Jessica L LarsonGuo-Cheng Yuan
Mar 24, 2017·PloS One·Markus RiesterFranziska Michor
May 28, 2019·Frontiers in Genetics·Allison BirnbaumHua Bai

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Methods Mentioned

BETA
ChIP-seq
ChIPseq

Software Mentioned

Roadmap
CisGenome
BEDTools
DAVID
ENCODE

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