染色质重塑蛋白BPTF是核小体重塑因子复合体(NURF)最大的亚基，通过与其它转录因子结合，将NURF招募到启动子区，调控核小体定位促进基因表达，但其在胚胎发育中的功能所知甚少。在脊椎动物原肠期，来自于腹侧中胚层的信号分子会促进神经外胚层分化为前部神经和后部神经组织。初步研究表明，BPTF及其介导的染色体重塑在前后神经图式形成中有重要作用。Smad2/3通过与染色质重塑蛋白BPTF协同作用，改变靶基因wnt8a启动子区核小体密度，增强wnt8a转录，促进神经外胚层后部化。但是，神经外胚层后部化过程中BPTF所介导的全基因组水平核小体位置具有怎样的动态变化？BPTF还可以与哪些转录因子相互作用影响染色质重塑？这些重要的问题均有待回答。本项目将围绕这些明确的科学问题，阐明脊椎动物神经后部化过程中BPTF调控染色质重塑的功能及分子机制。

The chromatin remodeling protein BPTF (Bromodomain PHD-finger Transcription Factor) is proviously identified by us as a Smad2 binding protein. BPTF, the largest NURF subunit, recruits NURF complex to specific DNA squence by binding with other transcription factors and then regulates gene expression by remodeling nucleosome sliding. During vertebrate gastrulation, “posteriorizing” signal from the ventral mesoderm converts already neuralized tissue to more posterior neural tissues. We find that, in zebrafish embryos, bptf plays crucial roles during the patterning of the anterior vs. the posterior neuroectoderm. Bptf and TGF-β/Smad2 mediate nucleosome remodeling to regulate wnt8a expression and hence neural posteriorization. However, little is known about the genome-wide remodeling of nucleosome positions mediated by BPTF during neural ectodermal posteriorization. Furthermore, whether Bptf functionally and physically interacts with other transcription factors to regulate nucleosome remodeling also remains unknown. Our project will elucidate the molecular mechanism of BPTF-mediated dynamic changes of chromatin higher-order structure in neural ectodermal posteriorization.