The emergence of a transcriptional silencer underlying the loss of a morphological trait

形态多样性和构成形态多样性的离散性状的变异在很大程度上是发育基因调控变化的结果。值得注意的是，这些基因调控序列的变异推动了基因表达的进化变化。尤其是转录增强子对特定的转录因子作出反应，并决定何时、何地以及转录多少发育基因。在进化文献中，解释增强子活性变化的主要焦点是这些转录因子的结合位点的转换。然而，最近有人提出，增强子序列的可及性由染色质紧致程度决定，也可以解释增强子活性的变化，从而调节基因表达。然而，这个调控水平，染色质的可及性，还没有从这个进化的角度进行检查。本提案试图通过研究染色质可及性在一种离散的形态特征--果蝇(果蝇)翼尖的色素斑点--进化中的作用来弥合这一差距。也就是说，我们已经在色素沉着基因黄色调节区的可及性方面发现了有趣的变化，在斑点物种和继发性失去斑点的物种之间。黄色表达是斑点形成的基础，其表达的变异代表着解释翅膀色素多样性的一个重要进化节点。结合转基因果蝇的报告分析和这些区域的基因组图谱(ATAC-SEQ，CHIP-SEQ)，我们将破译在进化转变过程中染色质可及性的变化可能通过哪些分子机制调节基因的表达。

Morphological diversity and the variation in discrete traits that composes it result, to a large extent, from changes in the regulation of developmental genes. Notably, variation in the regulatory sequences of these genes fuels evolutionary changes in gene expression. Transcriptional enhancers in particular respond to specific transcription factors and determine when, where and how much developmental genes are transcribed. The main focus in the evolutionary literature to explain the variation of enhancer activities is the turnover of binding sites for these transcription factors. It was recently suggested, however, that the accessibility of enhancer sequences, determined by the degree of chromatin compaction, may also explain the variation of enhancer activities and thereby modulate gene expression. Yet, this regulatory level, chromatin accessibility, has not been examined from this evolutionary standpoint. The present proposal attempts to bridge this gap by studying the role of chromatin accessibility in the evolution of a discrete morphological character, a pigmentation spot at the tip of the wing in flies (Drosophila). Namely, we have identify intriguing changes in the accessibility in the regulatory regions of the pigmentation gene yellow, between a spotted species and a species that has secondarily lost its spot. Yellow expression underlies the formation of the spot, and variation in its expression represent an important evolutionary node explaining wing pigmentation diversity. Combining reporter assays in transgenic Drosophila and genomic profiling (ATAC-seq, ChiP-seq) of these regions, we will decipher by which molecular mechanisms changes of chromatin accessibility may have modulated the expression of a gene during an evolutionary transition.