Miranda Paige, Enkhmandakh Badam, Bayarsaihan Dashzeveg
Cleft Palate Craniofac J. 2018 Jul;55(6):865-870. doi: 10.1597/15-214. Epub 2018 Feb 26.
The aim of this study is to define the candidate target genes for TFII-I and AP2α regulation in neural crest progenitor cells.
The GTF2I and GTF2IRD1 genes encoding the TFII-I family of transcription factors are prime candidates for the Williams-Beuren syndrome, a complex multisystem disorder characterized by craniofacial, skeletal, and neurocognitive deficiencies. AP2α, a product of the TFAP2A gene, is a master regulator of neural crest cell lineage. Mutations in TFAP2A cause branchio-oculo-facial syndrome characterized by dysmorphic facial features and orofacial clefts. In this study, we examined the genome-wide promoter occupancy of TFII-I and AP2α in neural crest progenitor cells derived from in vitro-differentiated human embryonic stem cells.
Our study revealed that TFII-I and AP2α co-occupy a selective set of genes that control the specification of neural crest cells.
The data suggest that TFII-I and AP2α may coordinately control the expression of genes encoding chromatin-modifying proteins, epigenetic enzymes, transcription factors, and signaling proteins.
本研究旨在确定神经嵴祖细胞中TFII-I和AP2α调控的候选靶基因。
编码TFII-I转录因子家族的GTF2I和GTF2IRD1基因是威廉姆斯-贝伦综合征的主要候选基因，该综合征是一种复杂的多系统疾病，其特征为颅面、骨骼和神经认知缺陷。TFAP2A基因的产物AP2α是神经嵴细胞谱系的主要调节因子。TFAP2A中的突变会导致以面部畸形和口面部裂为特征的鳃-眼-面综合征。在本研究中，我们检测了源自体外分化的人类胚胎干细胞的神经嵴祖细胞中TFII-I和AP2α在全基因组范围内的启动子占据情况。
我们的研究表明，TFII-I和AP2α共同占据了一组控制神经嵴细胞特化的基因。
数据表明，TFII-I和AP2α可能协同控制编码染色质修饰蛋白、表观遗传酶、转录因子和信号蛋白的基因的表达。
