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 控制基因组的酶、组蛋白伴侣蛋白和其他转录调节因子 功能。我们研究的许多蛋白质及其修饰在人类体内是失调的 疾病，包括癌症。尽管我们的实验室和其他实验室取得了相当大的进展，但至关重要的是 在我们对染色质调节的基本理解中，知识差距仍然存在。使用 此次米拉奖的续期，我们将继续研究染色质的功能 并解决染色质生物学中的三个最重要的基本问题： 1)组蛋白修饰酶和伴侣蛋白对染色质有何作用 组织和基因转录？2)最近发现的组蛋白PTM是如何 和阅读器结构域对基因转录的贡献？3)有什么规则可以遵循 组蛋白阅读器与核小体接触以及这些结合事件如何调节 染色质的下游事件？对于每个问题，我们突出显示以下几个示例 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.