Abstract
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.
Footnotes
Contact information: Nathan Palpant, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia, T: 61 0439 241 069, E: n.palpant{at}uq.edu.au, Mikael Bodén, School of Chemistry and Molecular Biology, The University of Queensland, Brisbane, Australia, T: 61 07 336 51307, E: m.boden{at}uq.edu.au