Cited by 314Genomics and Chromatin DynamicsDevelopmental Biology and Gene RegulationEpigenetics and DNA Methylation

Epigenomic annotation of enhancers predicts transcriptional regulators of human neural crest

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Rada-Iglesias, Alvaro, Bajpai, Ruchi, Prescott, Sara, Brugmann, Samantha A., Swigut, Tomek, Wysocka, Joanna·2012·Cell stem cell

Abstract

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.

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Crossref · 10.1016/j.stem.2012.07.006

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Authors
Rada-Iglesias, A., Bajpai, R., Prescott, S., Brugmann, S. A., Swigut, T., & Wysocka, J.
Affiliations
Stanford Medicine (US)
Corresponding author
Wysocka, Joanna
Venue
Cell stem cell
Publisher
Elsevier BV
Published
2012-11
Volume
11
Issue
5
Pages
633-648
ISSN
  • 1875-9777 (ISSN-L)
  • 1934-5909
OpenAlex
W2048350099
Cited by
314
References
62
Citations by year
2026: 10 · 2025: 17 · 2024: 13 · 2023: 18 · 2022: 22 · 2021: 28 · 2020: 43 · 2019: 28 · 2018: 22 · 2017: 18 · 2016: 24 · 2015: 20 · 2014: 26 · 2013: 25
FWCI
9.12
Type
journal article
Language
en
Open access
Locations
  • Cell stem cell (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Foundation for the National Institutes of Health
  • W. M. Keck Foundation
  • Siebel Scholars Foundation
  • National Institutes of Health (5p30de020750-02)
  • National Institute of General Medical Sciences (R01GM095555)
  • National Institute of Dental and Craniofacial Research (P30 DE020750)
  • Core Research for Evolutional Science and Technology
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Keywords
neural crest cells, enhancers, cis-regulatory elements, transcription factor binding, TFAP2A, NR2F1, NR2F2, histone modifications, P300, H3K27ac, human embryonic stem cell differentiation, craniofacial development, sequence constraints, chick embryo
MeSH terms
Animals, Cell Differentiation, Chick Embryo, Chromatin, Enhancer Elements, Genetic, Gene Expression Regulation, Humans, Neural Crest, Transcription Factors, Epigenesis, Genetic, Chromatin Immunoprecipitation, Transcription Factor AP-2, COUP Transcription Factor II, COUP Transcription Factor I, Embryonic Stem Cells

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