TY - JOUR T1 - Conserved epigenetic regulatory logic infers 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 - Yuliangzi Sun AU - Brad Balderson AU - Carles Boix AU - Guangdun Peng AU - Naihe Jing AU - Yuliang Wang AU - Manolis Kellis 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 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/10/09/635516.abstract N2 - Determining genes orchestrating cell differentiation in development and disease remains a fundamental goal of cell biology. This study establishes a genome-wide metric based on the gene-repressive tri-methylation of histone 3 lysine 27 (H3K27me3) across hundreds of diverse cell types to identify genetic regulators of cell differentiation. We introduce a computational method, TRIAGE, that uses discordance between gene-repressive tendency and expression to identify genetic drivers of cell identity. We apply TRIAGE to millions of genome-wide single-cell transcriptomes, diverse omics platforms, and eukaryotic cells and tissue types. Using a wide range of data, we validate TRIAGE’s performance for identifying cell-type specific regulatory factors across diverse species including human, mouse, boar, bird, fish, and tunicate. Using CRISPR gene editing, we use TRIAGE to experimentally validate RNF220 as a regulator of Ciona cardiopharyngeal development and SIX3 as required for differentiation of endoderm in human pluripotent stem cells. A record of this paper’s Transparent Peer Review process is included in the Supplemental Information.Competing Interest StatementThe authors have declared no competing interest. ER -