Histone modification profiles characterize function-specific gene regulation.

Chromatin modification is ubiquitous in gene regulation. Despite much effort, a systematic investigation is needed to understand whether each modification has a unique property depending on the function of its associated genes. Here, we show that consideration of function-specific histone modification profiles is important for accurate prediction of gene expression levels, and is maintained across cell types. The performance improvement is thought to originate from the association between modifications and gene expression levels for each biological function. The varying relationship between histone modifications and gene expression levels can be partly explained by considering function-specific PolII recruitment mechanisms, and is supported by more accurate predictions of PolII occupancies with function-specific modification profiles. We suggest that the function-specific binding of transcription factors and chromatin regulators may explain similar gene regulatory mechanisms, such as function-specific PolII recruitment, in each functional gene set. Our study demonstrates that each histone modification has a different characteristic according to the function of its associated genes; thus, different combinations of histone modification profiles characterize function-specific gene regulation. The current analysis is available on our web server (biodb.kaist.ac.kr/impohis).