RT Journal Article
SR Electronic
T1 Epigenomic and 3D genome architecture in naïve and primed human embryonic stem cell states
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 181123
DO 10.1101/181123
A1 Stephanie L. Battle
A1 Naresh Doni Jayavelu
A1 Robert N. Azad
A1 Jennifer Hesson
A1 Faria N. Ahmed
A1 Joseph A. Zoller
A1 Julie Mathieu
A1 Hannele Ruohola-Baker
A1 Carol B. Ware
A1 R. David Hawkins
YR 2017
UL http://biorxiv.org/content/early/2017/08/26/181123.abstract
AB During mammalian embryogenesis changes in morphology and gene expression are concurrent with epigenomic reprogramming. Using human embryonic stem cells representing the pre-implantation blastocyst (naïve) and post-implantation epiblast (primed), our data demonstrate that a substantial portion of known human enhancers are pre-marked by H3K4me1 in naïve cells, providing an enhanced open chromatin state in naïve pluripotency. The naïve enhancer repertoire occupies nine percent of the genome, three times that of primed cells, and can exist in broad chromatin domains over fifty kilobases. Enhancer chromatin states are largely poised. Seventy-seven percent of naïve enhancers are decommissioned in a stepwise manner as cells become primed. While primed topological associated domains are unaltered upon differentiation, naïve domains expand across primed boundaries, impacting three dimensional genome architecture. Differential topological associated domain edges coincide with naïve H3K4me1 enrichment. Our results suggest that naïve-derived cells have a chromatin landscape reflective of early embryogenesis.