Chromatin remodeling and expression dynamics reveal conserved and species-specific regulation during mouse and chicken limb development [ATAC-seq]. Chromatin remodeling and expression dynamics reveal conserved and species-specific regulation during mouse and chicken limb development [ATAC-seq]

Understanding the origin of morphological diversity across vertebrates is central to evolutionary developmental biology. cis-regulatory elements (CRE) such as enhancers and promoters interpret precise spatiotemporal cues to control and coordinate gene expression. To get insights into both conserved and species-specific variations during early limb patterning and outgrowth, we leverage genome-wide comprehensive assessment of chromatin accessibility and transcriptional changes during mouse forelimb and chicken wing bud development. Our analysis reveals temporal modulation of chromatin accessibility and expression as well as their temporal relationship during the progression of mouse forelimb and chicken wing bud development. Transcription factor binding site enrichment analysis and putative TF occupancy as inferred by integrating TF binding motifs and chromatin accessibility information reveal temporal TF-DNA interactions during forelimb/wing bud patterning. Finally, the integration of accessibility, expression, and TF binding site information allowed to identify candidate gene targets of HAND2 and GLI3 that include conserved as well as species-specific transcriptional regulator-gene interactions. Overall design: ATAC-seq analysis of developing mouse forelimb and chicken wing buds. Raw data of E10.5 and E11.5 developmental stages were previously submitted in GEO under GSE126292 (GSM3595750-GSM3595753).

解析脊椎动物形态多样性的起源，是进化发育生物学的核心研究议题。顺式调控元件（cis-regulatory elements, CRE），例如增强子与启动子，能够精准解读时空信号，以调控并协调基因的表达。为探究早期肢体模式形成与向外生长过程中保守及物种特异性的变异规律，本研究针对小鼠前肢与鸡翅芽发育过程中的染色质可及性及转录组变化，开展全基因组范围的系统性评估。本研究的分析结果显示，在小鼠前肢与鸡翅芽的发育进程中，染色质可及性与基因表达均呈现时序性调控特征，且二者的动态变化存在明确的时序关联。通过转录因子结合位点富集分析，以及整合转录因子结合基序与染色质可及性信息推断得到的潜在转录因子结合占据情况，本研究揭示了前肢/鸡翅芽模式形成过程中转录因子与DNA的时序性互作模式。最后，通过整合染色质可及性、基因表达及转录因子结合位点信息，本研究鉴定出HAND2与GLI3的候选靶基因，其中既包含保守的转录调控因子-基因互作关系，也存在物种特异性的调控模式。整体实验设计：针对发育中的小鼠前肢与鸡翅芽开展转座酶可及性测序（ATAC-seq）分析。胚胎发育第10.5天（E10.5）与第11.5天（E11.5）阶段的原始数据此前已提交至GEO数据库（Gene Expression Omnibus），数据集编号为GSE126292，对应样本号为GSM3595750至GSM3595753。