Epigenetic Regulation of Muscle Differentiation by the Chromatin Remodeling Protein ING2

染色质重塑是一种控制细胞增殖和分化的表观遗传机制，是发育和成年个体的基础。我研究项目的一个主要重点是了解染色质重塑如何促进细胞分化。以肌肉细胞分化（或肌发生）为模型，我们发现染色质重塑蛋白ING2促进肌肉分化。我们的数据表明，ING2可能与Brg1-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ING2是sumoylation的靶标，其中SUMO分子可逆地附着在ING2上。我们的初步数据表明，ING2可能在肌肉细胞中被介导，从而抑制了ING2促进肌肉分化的能力。因此，我们假设ING2与Brg1-SWI/SNF多蛋白复合物的相互作用导致肌原素的激活，肌原素是肌肉分化的主要调节因子，而sumoylation对ING2促进肌原素表达和肌肉分化产生负面影响。

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.  We will determine the ability of ING2 to interact with the Brg1 complex, specifically on promoter of the myogenin gene in the myogenic C2C12 cells during muscle differentiation. We will also determine if the interaction between ING2 and the Brg1-SWI/SNF complex is important for muscle differentiation. Moreover, we will determine the role of sumoylation in regulating ING2 function in differentiation using SUMO loss of function and gain of function approaches. Taken together, we will understand ING2 functionality and the role of chromatin remodeling in muscle and cell differentiation in general.