Epigenomic Annotation of Enhancers Predicts Transcriptional Regulators of Human Neural Crest

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 m...

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Bibliographic Details
Published in:Cell stem cell 2012-11, Vol.11 (5), p.633-648
Main Authors: Rada-Iglesias, Alvaro, Bajpai, Ruchi, Prescott, Sara, Brugmann, Samantha A., Swigut, Tomek, Wysocka, Joanna
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Cell Differentiation
Cell differentiation, maturation, development, hematopoiesis
Cell physiology
Chick Embryo - metabolism
Chromatin - metabolism
Chromatin Immunoprecipitation
COUP Transcription Factor I - genetics
COUP Transcription Factor I - metabolism
COUP Transcription Factor II - genetics
COUP Transcription Factor II - metabolism
Embryonic Stem Cells - cytology
Embryonic Stem Cells - metabolism
Enhancer Elements, Genetic
Epigenesis, Genetic
Fundamental and applied biological sciences. Psychology
Gene Expression Regulation
Humans
Molecular and cellular biology
Molecular genetics
Neural Crest - cytology
Neural Crest - metabolism
Transcription Factor AP-2 - genetics
Transcription Factor AP-2 - metabolism
Transcription Factors - genetics
Transcription Factors - metabolism
Transcription. Transcription factor. Splicing. Rna processing
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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. [Display omitted] ► 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 Chromatin profiling of hESC-derived neural crest identifies thousands of human enhancers conserved in the avian neural crest and provides a rich resource for studies of craniofacial development and disease.
ISSN:1934-5909
1875-9777
DOI:10.1016/j.stem.2012.07.006