Molecular mechanisms and cellular functions of the CpG island-binding protein SAMD1

CpG岛结合蛋白SAMD1的分子机制和细胞功能

• 批准号: 516068166
• 负责人: Dr. Robert Liefke
• 金额: --
• 依托单位: Institut für Molekularbiologie und Tumorforschung (IMT)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/516068166?language=en
• 关键词: Molecular; mechanisms; cellular; functions; CpG

Precise gene expression is essential for the proper functioning of cells in the body. We recently identified SAM domain-containing protein 1 (SAMD1) as a unique transcriptional regulator that acts at unmethylated CpG islands. SAMD1 is characterized by a CpG island-binding domain and a multimerizing SAM domain. It interacts with several chromatin regulatory proteins, including the histone demethylase KDM1A and the chromatin regulator L3MBTL3. Our work demonstrated that SAMD1 mainly functions as a transcriptional repressor and that its deletion leads to aberrant gene regulatory processes. SAMD1 is expressed in all tissues, implicating an abundant biological function, which is supported by embryonic lethality of mice that lack SAMD1. Although our initial characterization of SAMD1 already provided several fascinating insights, many aspects of SAMD1’s function remain to be explored. In our research, it is our goal to characterize the molecular mechanisms and cellular functions of SAMD1. In this research proposal, we aim 1) to elucidate the mechanisms that drive SAMD1 chromatin association, 2) to investigate the molecular process facilitated upon SAMD1’s repressive activity, 3) to assess the potential role of SAMD1’s multimerization ability in long-range chromatin interaction and 4) to investigate the role of SAMD1 during neuronal differentiation processes. We expect from this work novel insights about the molecular and cellular functions of this unique chromatin regulator, which will help to understand its function during gene regulatory processes and how its dysregulation may lead to human diseases.

精确的基因表达对于体内细胞的正常功能至关重要。我们最近发现SAM结构域包含蛋白1（SAMD1）作为一个独特的转录调控，在未甲基化的CpG岛的行为。SAMD1的特征在于CpG岛结合结构域和多聚化SAM结构域。它与几种染色质调节蛋白相互作用，包括组蛋白去甲基化酶KDM1A和染色质调节因子L3MBTL3。我们的工作表明，SAMD1主要作为一个转录抑制因子，它的缺失导致异常的基因调控过程。SAMD1在所有组织中表达，暗示了丰富的生物学功能，这得到了缺乏SAMD1的小鼠的胚胎致死率的支持。虽然我们对SAMD1的初步表征已经提供了一些令人着迷的见解，但SAMD1功能的许多方面仍有待探索。在我们的研究中，我们的目标是表征SAMD1的分子机制和细胞功能。在这项研究计划中，我们的目标是1）阐明驱动SAMD1染色质缔合的机制，2）研究SAMD1的抑制活性促进的分子过程，3）评估SAMD1的多聚化能力在长距离染色质相互作用中的潜在作用，以及4）研究SAMD1在神经元分化过程中的作用。我们期望从这项工作中获得关于这种独特的染色质调节剂的分子和细胞功能的新见解，这将有助于了解其在基因调控过程中的功能以及其失调如何导致人类疾病。