CHD7 cooperates with PBAF to control multipotent neural crest formation

Ruchi Bajpai, Denise A. Chen, Alvaro Rada-Iglesias, Junmei Zhang, Yiqin Xiong, Jill Helms, Ching-Pin Chang, Yingming Zhao, Tomek Swigut, Joanna Wysocka

Research output: Contribution to journalArticle

312 Citations (Scopus)

Abstract

Heterozygous mutations in the gene encoding the CHD (chromodomain helicase DNA-binding domain) member CHD7, an ATP-dependent chromatin remodeller homologous to the Drosophila trithorax-group protein Kismet, result in a complex constellation of congenital anomalies called CHARGE syndrome, which is a sporadic, autosomal dominant disorder characterized by malformations of the craniofacial structures, peripheral nervous system, ears, eyes and heart. Although it was postulated 25 years ago that CHARGE syndrome results from the abnormal development of the neural crest, this hypothesis remained untested. Here we show that, in both humans and Xenopus, CHD7 is essential for the formation of multipotent migratory neural crest (NC), a transient cell population that is ectodermal in origin but undergoes a major transcriptional reprogramming event to acquire a remarkably broad differentiation potential and ability to migrate throughout the body, giving rise to craniofacial bones and cartilages, the peripheral nervous system, pigmentation and cardiac structures. We demonstrate that CHD7 is essential for activation of the NC transcriptional circuitry, including Sox9, Twist and Slug. In Xenopus embryos, knockdown of Chd7 or overexpression of its catalytically inactive form recapitulates all major features of CHARGE syndrome. In human NC cells CHD7 associates with PBAF (polybromo-and BRG1-associated factor-containing complex) and both remodellers occupy a NC-specific distal SOX9 enhancer and a conserved genomic element located upstream of the TWIST1 gene. Consistently, during embryogenesis CHD7 and PBAF cooperate to promote NC gene expression and cell migration. Our work identifies an evolutionarily conserved role for CHD7 in orchestrating NC gene expression programs, provides insights into the synergistic control of distal elements by chromatin remodellers, illuminates the patho-embryology of CHARGE syndrome, and suggests a broader function for CHD7 in the regulation of cell motility.

Original languageEnglish (US)
Pages (from-to)958-962
Number of pages5
JournalNature
Volume463
Issue number7283
DOIs
StatePublished - Feb 18 2010
Externally publishedYes

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Neural Crest
CHARGE Syndrome
Peripheral Nervous System
Xenopus
Chromatin
Cell Movement
DNA Helicases
Gene Expression
Gastropoda
Embryology
Pigmentation
Genes
Cartilage
Embryonic Development
Ear
Embryonic Structures
Adenosine Triphosphate
Bone and Bones
Mutation
Population

ASJC Scopus subject areas

  • General

Cite this

Bajpai, R., Chen, D. A., Rada-Iglesias, A., Zhang, J., Xiong, Y., Helms, J., ... Wysocka, J. (2010). CHD7 cooperates with PBAF to control multipotent neural crest formation. Nature, 463(7283), 958-962. https://doi.org/10.1038/nature08733

CHD7 cooperates with PBAF to control multipotent neural crest formation. / Bajpai, Ruchi; Chen, Denise A.; Rada-Iglesias, Alvaro; Zhang, Junmei; Xiong, Yiqin; Helms, Jill; Chang, Ching-Pin; Zhao, Yingming; Swigut, Tomek; Wysocka, Joanna.

In: Nature, Vol. 463, No. 7283, 18.02.2010, p. 958-962.

Research output: Contribution to journalArticle

Bajpai, R, Chen, DA, Rada-Iglesias, A, Zhang, J, Xiong, Y, Helms, J, Chang, C-P, Zhao, Y, Swigut, T & Wysocka, J 2010, 'CHD7 cooperates with PBAF to control multipotent neural crest formation', Nature, vol. 463, no. 7283, pp. 958-962. https://doi.org/10.1038/nature08733
Bajpai R, Chen DA, Rada-Iglesias A, Zhang J, Xiong Y, Helms J et al. CHD7 cooperates with PBAF to control multipotent neural crest formation. Nature. 2010 Feb 18;463(7283):958-962. https://doi.org/10.1038/nature08733
Bajpai, Ruchi ; Chen, Denise A. ; Rada-Iglesias, Alvaro ; Zhang, Junmei ; Xiong, Yiqin ; Helms, Jill ; Chang, Ching-Pin ; Zhao, Yingming ; Swigut, Tomek ; Wysocka, Joanna. / CHD7 cooperates with PBAF to control multipotent neural crest formation. In: Nature. 2010 ; Vol. 463, No. 7283. pp. 958-962.
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