TY - JOUR T1 - Comparative analysis of diverse cell states establishes an epigenetic basis for inferring regulatory genes governing cell identity JF - bioRxiv DO - 10.1101/635516 SP - 635516 AU - Woo Jun Shim AU - Enakshi Sinniah AU - Jun Xu AU - Burcu Vitrinel AU - Michael Alexanian AU - Gaia Andreoletti AU - Sophie Shen AU - Brad Balderson AU - Guangdun Peng AU - Naihe Jing AU - Yuliangzi Sun AU - Yash Chhabra AU - Yuliang Wang AU - Patrick P L Tam AU - Aaron Smith AU - Michael Piper AU - Lionel Christiaen AU - Quan Nguyen AU - Mikael Bodén AU - Nathan J. Palpant Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/05/18/635516.abstract N2 - Understanding genetic control of cell diversification is essential for establishing mechanisms controlling biological complexity. This study demonstrates that the a priori deposition of H3K27me3 associated with gene repression across diverse cell states provides a genome-wide metric that enriches for genes governing fundamental mechanisms underlying biological complexity in differentiation, morphogenesis, and disease. We use this metric in combination with more than 1 million genome-wide data sets from diverse omics platforms to identify cell type specific regulatory mechanisms underlying diverse organ systems from species across the animal kingdom. From this analysis, we identify and genetically validate multiple novel genes controlling development in diverse chordates including humans and the tunicate, Ciona robusta. This study demonstrates that the conservation of epigenetic regulatory logic provides an effective strategy for utilizing large, diverse genome-wide data to establish quantitative basic principles of cell states to infer cell-type specific mechanisms that underpin the complexity of biological systems. ER -