Mechanisms of chromatin and transcriptional regulation

我们的长期目标是揭示组蛋白修饰的分子机制， 酶、组蛋白伴侣和其他控制基因组的转录调节因子 功能我们研究的许多蛋白质及其修饰在人类中都是失调的。 疾病，包括癌症。尽管我们的实验室和其他人取得了相当大的进展， 在我们对染色质调控的基本理解方面仍然存在知识差距。与 MIRA奖的延续，我们将继续研究染色质的功能 调节和解决染色质生物学中三个最重要的基本问题： 1)组蛋白修饰酶和分子伴侣如何影响染色质 组织和基因转录？2)最近发现的组蛋白PTM 和阅读器结构域对基因转录有贡献吗3)有什么规则 组蛋白阅读器与核小体结合，这些结合事件如何调节 染色质中的下游事件对于每一个问题，我们强调几个例子， 我们正在进行的研究类型，并描述它们将如何推动该领域的发展。

Our long-term goal has been to reveal the molecular mechanisms of histone-modifying enzymes, histone chaperones and other transcriptional regulators that control genome function. Many of the proteins and their modifications we study are dysregulated in human disease, including cancer. Despite considerable progress by our lab and others, crucial knowledge gaps remain in our fundamental understanding of chromatin regulation. With the renewal of this MIRA award, we will continue our studies into the function of chromatin regulators and address three of the foremost fundamental questions in chromatin biology: 1) How do histone-modifying enzymes and chaperones contribute to chromatin organization and gene transcription? 2) How do more recently discovered histone PTMs and reader domains contribute to gene transcription? 3) What are the rules by which histone readers engage nucleosomes and how do these binding events regulate downstream events in chromatin? For each question, we highlight several examples of the types of studies we are pursuing and describe how they will advance the field.