High Resolution Epigenomic Atlas of Early Human Craniofacial Development

Defects in patterning during human embryonic development frequently result in craniofacial abnormalities. The gene regulatory programs that build the craniofacial complex are likely controlled by information located between genes and within intronic sequences. However, systematic identification of regulatory sequences important for forming the human face have not been performed. Here we describe comprehensive epigenomic annotations from human embryonic craniofacial tissues and systematic comparisons with multiple tissues and cell types. We identified thousands of tissue-specific craniofacial regulatory sequences and likely causal regions for rare craniofacial abnormalities. We demonstrate significant enrichment of common variants associated with orofacial clefting in enhancers active early in embryonic development, while those associated with normal facial variation are enriched near the end of the embryonic period. These data are provided in easily accessible formats for both craniofacial researchers and clinicians to aid future experimental design and interpretation of non-coding variation in those affected by craniofacial abnormalities.

人类胚胎发育过程中图案形成缺陷常常导致颅面畸形的产生。构建颅面复合体的基因调控程序可能受到位于基因之间以及内含子序列中的信息的调控。然而，对形成人类面部至关重要的调控序列的系统鉴定尚未进行。在本研究中，我们描述了从人类胚胎颅面组织中提取的全面表观基因组注释，并与多种组织和细胞类型进行了系统比较。我们鉴定了数千个组织特异性的颅面调控序列以及罕见颅面畸形的可能因果区域。我们发现，与胚胎早期发育中活跃的增强子中相关的常见变异在口面部裂隙中显著富集，而与正常面部变异相关的变异则在胚胎期末期附近富集。这些数据以易于获取的格式提供，旨在协助颅面研究人员和临床医生进行未来的实验设计，并有助于解读受颅面畸形影响者的非编码变异。