The conserved MLR COMPASS-like complexes are histone modifiers that are recruited by a variety of transcription factors to enhancer regions where they act as necessary epigenetic tools for enhancer establishment and function. A critical in vivo target of the Drosophila MLR complex is the bantam miRNA that regulates cell survival and functions in feedback regulation of cellular signaling pathways during development. We determine that loss of Drosophila MLR complex function in developing wing and eye imaginal discs results in growth and patterning defects that are sensitive to bantam levels. Consistent with an essential regulatory role in modulating bantam transcription, the MLR complex binds to tissue-specific bantam enhancers and contributes to fine-tuning expression levels during larval tissue development. In wing imaginal discs, the MLR complex attenuates bantam enhancer activity by negatively regulating expression; whereas, in differentiating eye discs, the complex exerts either positive or negative regulatory activity on bantam transcription depending on cell fate. Furthermore, while the MLR complex is not required to control bantam levels in undifferentiated eye cells anterior to the morphogenetic furrow, it serves to prepare critical enhancer control of bantam transcription for later regulation upon differentiation. Our investigation into the transcriptional regulation of a single target in a developmental context has provided novel insights as to how the MLR complex contributes to the precise timing of gene expression, and how the complex functions to help orchestrate the regulatory output of conserved signaling pathways during animal development.

保守的MLR COMPASS样复合物是组蛋白修饰物，其被多种转录因子募集到增强子区域，在其中它们充当增强子建立和功能的必要表观遗传学工具。果蝇MLR复合物的关键体内靶标是矮脚鸡miRNA，其在发育过程中调节细胞存活并在细胞信号通路的反馈调节中起作用。我们确定果蝇MLR复杂功能在发展的机翼和眼睛的想象中的圆盘的丧失会导致对矮脚鸡水平敏感的生长和图案缺陷。MLR复合物与调节矮脚鸡转录中的重要调节作用一致，可与组织特异性矮脚鸡结合增强子，并有助于在幼虫组织发育过程中微调表达水平。在机翼的假想椎间盘中，MLR复合物通过负向调节表达减弱了矮脚鸡增强子的活性。而在区分视盘中，该复合物根据细胞命运对矮脚鸡转录发挥正调控作用或负调控作用。此外，虽然不需要MLR复合物来控制形态发生犁沟前未分化眼细胞中的矮脚鸡水平，但它可用于制备关键的矮脚鸡增强剂控制转录，以便以后进行分化调控。我们对发育环境中单个靶标转录调控的研究为MLR复合物如何促进基因表达的精确时机，以及该复合物如何发挥功能来协调动物体内保守信号通路的调控输出提供了新颖的见解。发展。