TY - JOUR T1 - Chromatin accessibility dynamics of myogenesis at single cell resolution JF - bioRxiv DO - 10.1101/155473 SP - 155473 AU - Hannah A. Pliner AU - Jonathan Packer AU - José L. McFaline-Figueroa AU - Darren A. Cusanovich AU - Riza Daza AU - Sanjay Srivatsan AU - Xiaojie Qiu AU - Dana Jackson AU - Anna Minkina AU - Andrew Adey AU - Frank J. Steemers AU - Jay Shendure AU - Cole Trapnell Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/06/26/155473.abstract N2 - Over a million DNA regulatory elements have been cataloged in the human genome, but linking these elements to the genes that they regulate remains challenging. We introduce Cicero, a statistical method that connects regulatory elements to target genes using single cell chromatin accessibility data. We apply Cicero to investigate how thousands of dynamically accessible elements orchestrate gene regulation in differentiating myoblasts. Groups of co-accessible regulatory elements linked by Cicero meet criteria of “chromatin hubs”, in that they are physically proximal, interact with a common set of transcription factors, and undergo coordinated changes in histone marks that are predictive of gene expression. Pseudotemporal analysis revealed a subset of elements bound by MYOD in myoblasts that exhibit early opening, potentially serving as the initial sites of recruitment of chromatin remodeling and histone-modifying enzymes. The methodological framework described here constitutes a powerful new approach for elucidating the architecture, grammar and mechanisms of cis-regulation on a genome-wide basis. ER -