PT  - JOURNAL ARTICLE
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
TI  - Chromatin accessibility dynamics of myogenesis at single cell resolution
AID  - 10.1101/155473
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 155473
4099  - http://biorxiv.org/content/early/2017/06/26/155473.short
4100  - http://biorxiv.org/content/early/2017/06/26/155473.full
AB  - 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.