ATAC-seq in Xenopus laevis gastrula stage

The hypothesis being tested is that loss of competence to respond to inductive signals is mediated by loss of chromatin accessibility. This dataset describes analysis of an Assay for Transposase-Accessible Chromatin followed by sequencing (ATAC-Seq) approach to evaluate genome-wide changes in chromatin accessibility in Xenopus laevis. ATAC-seq identifies ~70,000 accessible regions at early and late gastrula stage; normalized read counts from 3 biological replicates at early (stage 10) and late (stage 12) gastrula stage are presented here. Genome wide distribution of accessible peaks, list of promoters with changes in accessibility between stage 10 and stage 12, comparison with previously published p300 ChIP-seq data to identify putative cis-regulatory modules (pCRMs), comparison of promoter accessibility and gene expression, identification of transcription factor binding motifs associated with pCRMs, and functional gene annotation analyses are presented. Promoters for dorsal genes (Sia and Xnr3) that have lost competence to respond to Wnt signaling are not accessible at the early gastrula stage but competence can be maintained by inhibiting HDACs and increasing histone acetylation at these promoters. Promoters for regulators of mesoderm and neural crest induction maintain accessibility throughout gastrulation despite the loss of competence to respond to their respective inductive signals, suggesting context-dependent regulation of competence. However, 279 promoters lose accessibility at stage 12 and are associated with transcription factors that regulate early development. Accessibility at ≥ 1800 promoter-distal pCRMs is also reduced by the end the gastrula stage, and these pCRMs are frequently near promoters for transcription factors that regulate early development, including homeobox genes. Motif analysis (HOMER) shows marked enrichment for binding sites for pluripotency factors of the Sox, Oct, and KLF transcription factor families, as well as for Fox, Grainyhead-like, and Zic transcription factors.本研究验证的假说为：细胞对诱导信号产生响应的能力丧失，是由染色质可及性降低所介导的。本数据集针对非洲爪蟾（Xenopus laevis）开展相关分析，采用转座酶可及性染色质测序（Assay for Transposase-Accessible Chromatin followed by sequencing，简称ATAC-Seq）技术，对其全基因组范围内的染色质可及性变化进行评估。该技术在早期与晚期原肠胚阶段共鉴定到约7万个染色质可及区域；本文展示了早期（第10期）与晚期（第12期）原肠胚阶段的3次生物学重复样本的标准化读段计数结果。本数据集包含如下分析内容：染色质可及峰的全基因组分布、第10期与第12期原肠胚阶段染色质可及性存在差异的启动子列表、与已发表的p300染色质免疫共沉淀测序（Chromatin Immunoprecipitation Sequencing，简称ChIP-seq）数据比对以鉴定潜在顺式调控模块（putative cis-regulatory modules，简称pCRMs）、启动子可及性与基因表达水平的关联分析、与pCRMs相关的转录因子结合基序鉴定，以及功能基因注释分析。丧失Wnt信号通路响应能力的背侧基因（Sia与Xnr3）的启动子在早期原肠胚阶段不具备染色质可及性，但通过抑制组蛋白去乙酰化酶（Histone Deacetylases，简称HDACs）并增强这些启动子区域的组蛋白乙酰化水平，可维持其响应能力。中胚层与神经嵴诱导调控因子的启动子，尽管丧失了对各自诱导信号的响应能力，但在整个原肠胚发育过程中始终保持可及性，这提示细胞响应能力的调控具有上下文依赖性。不过，有279个启动子在第12期原肠胚阶段丧失了染色质可及性，这些启动子与调控早期发育的转录因子相关。在原肠胚发育末期，至少1800个位于启动子远端的pCRMs的染色质可及性也出现降低，且这些pCRMs通常紧邻调控早期发育的转录因子基因的启动子，其中包括同源框基因家族。基序分析（HOMER）结果显示，Sox、Oct与KLF转录因子家族的多能性因子结合位点，以及Fox、Grainyhead-like与Zic转录因子的结合位点均出现显著富集。