RT Journal Article
SR Electronic
T1 Chromatin accessibility dynamics of myogenesis at single cell resolution
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 155473
DO 10.1101/155473
A1 Hannah A. Pliner
A1 Jonathan Packer
A1 José L. McFaline-Figueroa
A1 Darren A. Cusanovich
A1 Riza Daza
A1 Sanjay Srivatsan
A1 Xiaojie Qiu
A1 Dana Jackson
A1 Anna Minkina
A1 Andrew Adey
A1 Frank J. Steemers
A1 Jay Shendure
A1 Cole Trapnell
YR 2017
UL http://biorxiv.org/content/early/2017/06/26/155473.abstract
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.