Regulation of chromatin accessibility by small non-coding RNAs

小非编码 RNA 调节染色质可及性

• 批准号: 2749384
• 金额: --
• 依托单位: University of East Anglia
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2749384
• 关键词: Regulation; chromatin; accessibility; small; non

Skeletal muscle is important for health and well-being throughout life. To understand better the factors that contribute to the maintenance of this important tissue, we study its development in the embryo. It is known that many of the genes and mechanisms that control embryo development are conserved across species and perform similar functions in adult organisms. This is also the case for small non-coding RNAs, called microRNAs, which are highly expressed in developing and mature skeletal muscles, where they can have a protective function, for example in ageing or disease. To discover the full potential of microRNAs for healthy muscles functional experiments are being used in early avian embryos in ovo. These showed that muscle specific microRNAs, so-called myomirs, negatively regulate the expression of crucial transcription factors and epigenetic regulators (Pax3, Gli3, BAF60a/b). This is essential to provide robustness to developmental timing during the progenitor to myoblast transition, and to stably establish the myogenic differentiation programme. The project will investigate further the role of myomirs for chromatin accessibility and thus the regulation of gene expression in embryo myogenesis. Using established experimental manipulations followed by genome-wide analysis using next generation sequencing, chromatin accessibility and identify novel cis-regulatory elements (CRE) will be characterised. These will be validated in vivo using time-lapse imaging and CRISPR-editing and their role in early muscle development will be tested.

骨骼肌是重要的健康和幸福的整个生命。为了更好地了解有助于维持这一重要组织的因素，我们研究了它在胚胎中的发育。众所周知，许多控制胚胎发育的基因和机制在物种间是保守的，并且在成年生物体中执行类似的功能。小的非编码RNA也是如此，称为microRNA，它们在发育和成熟的骨骼肌中高度表达，在那里它们可以具有保护功能，例如在衰老或疾病中。为了发现microRNA对健康肌肉的全部潜力，正在对早期鸟类卵内胚胎进行功能实验。这些结果表明，肌肉特异性microRNA，所谓的myomir，负调控关键转录因子和表观遗传调节因子（Pax 3，Gli 3，BAF 60 a/B）的表达。这对于在祖细胞向成肌细胞转变期间提供发育时间的稳健性以及稳定地建立肌源性分化程序是至关重要的。该项目将进一步研究myomirs对染色质可及性的作用，从而研究胚胎肌发生中基因表达的调节。使用已建立的实验操作，然后使用下一代测序进行全基因组分析，染色质可及性和识别新的顺式调控元件（CRE）将被表征。这些将使用延时成像和CRISPR编辑在体内进行验证，并测试它们在早期肌肉发育中的作用。