Epigenetic Regulation of Muscle Differentiation by the Chromatin Remodeling Protein ING2

染色质重塑蛋白 ING2 对肌肉分化的表观遗传调控

• 批准号: RGPIN-2015-06579
• 负责人: Bonni, Shirin
• 金额: $ 2.19万
• 依托单位: University of Calgary
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=629323
• 关键词: Epigenetic; Regulation; Muscle; Differentiation; Chromatin

Chromatin remodeling is an epigenetic mechanism that controls cell proliferation and differentiation, which are fundamental in the developing and adult individual. A major focus of my research program is to understand how chromatin remodeling contributes to cell differentiation. Using muscle cell differentiation (or myogenesis) as a model, we have found that the chromatin remodeling protein ING2 promotes muscle differentiation. Our data suggest that ING2 may cooperate with the Brg1-SW/SNF chromatin remodeling multiprotein complex to positively regulate cell differentiation. We have confirmed that ING2 is a target of sumoylation, where a SUMO molecule is attached reversibly to ING2. Our preliminary data suggest that ING2 might be sumoylated in muscle cells to suppress the ability of ING2 to promote muscle differentiation.  Thus, we hypothesize that the interaction of ING2 with the Brg1-SWI/SNF multiprotein complex leads to activation of myogenin, which is the master regulator of muscle differentiation, and that sumoylation negatively affects ING2 promotion of myogenin expression and hence muscle differentiation.

染色质重塑是控制细胞增殖和分化的表观遗传机制，其在发育和成年个体中是基本的。我的研究计划的一个主要重点是了解染色质重塑如何有助于细胞分化。使用肌肉细胞分化（或肌发生）作为模型，我们发现染色质重塑蛋白ING 2促进肌肉分化。我们的数据表明，ING 2可能与Brg 1-SW/SNF染色质重塑多蛋白复合物合作，积极调节细胞分化。我们已经证实ING 2是SUMO化的靶点，其中SUMO分子可逆地连接到ING 2。我们的初步数据表明，ING 2可能在肌肉细胞中被sumoylated，以抑制ING 2促进肌肉分化的能力。 因此，我们假设ING 2与Brg 1-SWI/SNF多蛋白复合物的相互作用导致肌细胞生成素的激活，肌细胞生成素是肌肉分化的主要调节因子，而SUMO化对ING 2促进肌细胞生成素表达和肌肉分化产生负面影响。