The homeodomain protein NK2 homeobox 2 (NKX2-2) is a transcription factor that plays a critical role in the control of cell fate specification and differentiation in many tissues. In the developing central nervous system, this developmentally important transcription factor functions as a transcriptional repressor that governs oligodendrocyte (OL) differentiation and myelin gene expression, but the roles of various NKX2-2 structural domains in this process are unclear. In this study, using in situ hybridization, immunofluorescence, and coimmunoprecipitation, we determined the structural domains that mediate the repressive functions of murine NKX2-2 and identified the transcriptional corepressors that interact with it in OL cells. Through in ovo electroporation in embryonic chicken spinal cords, we demonstrate that the N-terminal Tinman domain and C-terminal domain synergistically promote OL differentiation by recruiting distinct transcriptional corepressors, including enhancer of split Groucho 3 (GRG3), histone deacetylase 1 (HDAC1), and DNA methyltransferase 3 α (DNMT3A). We also observed that the NK2-specific domain suppresses the function of the C-terminal domain in OL differentiation. These findings delineate the distinct NKX2-2 domains and their roles in OL differentiation and suggest that NKX2-2 regulates differentiation by repressing gene expression via multiple cofactors and molecular mechanisms.

中文翻译：

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转录因子NKX2-2通过与转录共表达因子的域特异性相互作用来调节少突胶质细胞的分化。

同源域蛋白NK2同源盒2（NKX2-2）是一种转录因子，在许多组织的细胞命运规范和分化控制中起着关键作用。在发育中的中枢神经系统中，这种在发育上重要的转录因子起着转录抑制因子的作用，该转录抑制因子控制少突胶质细胞（OL）的分化和髓磷脂基因的表达，但是各种NKX2-2结构域在此过程中的作用尚不清楚。在这项研究中，我们使用原位杂交，免疫荧光和免疫共沉淀技术，确定了介导鼠NKX2-2阻遏功能的结构域，并确定了在OL细胞中与其相互作用的转录共受体。通过卵在胚胎鸡脊髓中的电穿孔，我们证明了N末端的Tinman域和C末端域通过募集不同的转录共受体来协同促进OL分化，包括分裂Groucho 3（GRG3），组蛋白脱乙酰基酶1（HDAC1）和DNA甲基转移酶3α（DNMT3A）的增强子。我们还观察到NK2特定域抑制OL分化中的C末端域的功能。这些发现描述了不同的NKX2-2域及其在OL分化中的作用，并表明NKX2-2通过多种辅助因子和分子机制抑制基因表达来调节分化。我们还观察到NK2特定域抑制OL分化中C末端域的功能。这些发现描述了不同的NKX2-2域及其在OL分化中的作用，并表明NKX2-2通过多种辅助因子和分子机制抑制基因表达来调节分化。我们还观察到NK2特定域抑制OL分化中的C末端域的功能。这些发现描述了不同的NKX2-2域及其在OL分化中的作用，并表明NKX2-2通过多种辅助因子和分子机制抑制基因表达来调节分化。