title: Computational inference of mRNA stability from histone modification and transcriptome profiles.
abstract: Histone modifications play important roles in regulating eukaryotic gene expression and have been used to model expression levels. Here, we present a regression model to systematically infer mRNA stability by comparing transcriptome profiles with ChIP-seq of H3K4me3, H3K27me3 and H3K36me3. The results from multiple human and mouse cell lines show that the inferred unstable mRNAs have significantly longer 3'Untranslated Regions (UTRs) and more microRNA binding sites within 3'UTR than the inferred stable mRNAs. Regression residuals derived from RNA-seq, but not from GRO-seq, are highly correlated with the half-lives measured by pulse-labeling experiments, supporting the rationale of our inference. Whereas, the functions enriched in the inferred stable and unstable mRNAs are consistent with those from pulse-labeling experiments, we found the unstable mRNAs have higher cell-type specificity under functional constraint. We conclude that the systematical use of histone modifications can differentiate non-expressed mRNAs from unstable mRNAs, and distinguish stable mRNAs from highly expressed ones. In summary, we represent the first computational model of mRNA stability inference that compares transcriptome and epigenome profiles, and provides an alternative strategy for directing experimental measurements.
authors.affiliation: Department of Bioinformatics, School of Life Science and Technology, Tongji University, 1239 Siping Road, Shanghai 20092, China.
authors.forename: Chengyang
authors.initials: C
authors.lastname: Wang
authors.forename: Rui
authors.initials: R
authors.lastname: Tian
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhao
authors.forename: Han
authors.initials: H
authors.lastname: Xu
authors.forename: Clifford A
authors.initials: CA
authors.lastname: Meyer
authors.forename: Cheng
authors.initials: C
authors.lastname: Li
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.forename: X Shirley
authors.initials: XS
authors.lastname: Liu
mesh_terms: D000818:Animals; D002460:Cell Line; D019295:Computational Biology / Q000379:methods*; D020869:Gene Expression Profiling; D006207:Half-Life; D006657:Histones / Q000378:metabolism*; D006801:Humans; D016014:Linear Models; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism; D020871:RNA Stability; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism*; D017423:Sequence Analysis, RNA; D059467:Transcriptome
chemical_list: D006657:Histones; D035683:MicroRNAs; D012333:RNA, Messenger