Cell Stem Cell
Volume 11, Issue 5, 2 November 2012, Pages 633-648
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Article
Epigenomic Annotation of Enhancers Predicts Transcriptional Regulators of Human Neural Crest

https://doi.org/10.1016/j.stem.2012.07.006Get rights and content
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Summary

Neural crest cells (NCC) are a transient, embryonic cell population characterized by unusual migratory ability and developmental plasticity. To annotate and characterize cis-regulatory elements utilized by the human NCC, we coupled a hESC differentiation model with genome-wide profiling of histone modifications and of coactivator and transcription factor (TF) occupancy. Sequence analysis predicted major TFs binding at epigenomically annotated hNCC enhancers, including a master NC regulator, TFAP2A, and nuclear receptors NR2F1 and NR2F2. Although many TF binding events occur outside enhancers, sites coinciding with enhancer chromatin signatures show significantly higher sequence constraint, nucleosomal depletion, correlation with gene expression, and functional conservation in NCC isolated from chicken embryos. Simultaneous co-occupancy by TFAP2A and NR2F1/F2 is associated with permissive enhancer chromatin states, characterized by high levels of p300 and H3K27ac. Our results provide global insights into human NC chromatin landscapes and a rich resource for studies of craniofacial development and disease.

Highlights

► Chromatin profiling identifies thousands of human NC enhancers ► Many enhancers are functionally conserved in the avian embryo NC ► Chromatin signatures predict novel NC transcriptional regulators ► TFAP2A and NR2F1/2 cooperate to promote permissive enhancer chromatin states

Cited by (0)

3

Present address: Center for Craniofacial Molecular Biology, Ostrow School of Dentistry and Department of Biochemistry and Molecular Biology, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA

4

Present address: Division of Plastic Surgery and Division of Developmental Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio 45229, USA

5

These authors contributed equally to this work