Expression of ID2 and ID4 is repressed by EGR2:NAB

ID1-4 (Inhibitor of DNA-binding) are members of the helix-loop-helix family of proteins that lack the basic amino acids responsible for DNA binding in basic HLH proteins. HLH domain-mediated heterodimerization of an ID protein with a basic HLH protein therefore acts as a natural dominant negative inhibitor of bHLH function by preventing DNA binding (Massari and Murre, 2000). ID proteins primarily interact with members of the E family of proteins, including E12, E47, HEB and E2-2, but also interact with other bHLH proteins. ID proteins promote cell cycle progression and cell migration, and restrict cellular senescence and the differentiation of a number of progenitor cell types, including oligodendrocytes (reviewed in Perk et al, 2005; Ling et al, 2014).
Expression of ID2 and ID4 is negatively regulated by an EGR2:NAB2 complex that is recruited to the EGR binding sites in the promoter. Repression of ID2 and ID4 during development is associated with increased promoter occupancy of the EGR2:NAB2 complex and may be effected through the recruitment of the NURD chromatin remodelling complex and histone deacetylases. NAB2 has been shown to interact with the CHD4 and CHD3 subunits of the NURD complex through its conserved CHD4-interacting domain (CID) (Mager et al, 2008; Srinivasan et al, 2006; Hung et al, 2012).

ID1-4（DNA结合抑制剂）是螺旋-环-螺旋蛋白家族的成员，它们缺乏基本氨基酸，这些氨基酸在基本HLH蛋白中负责DNA结合。因此，ID蛋白与基本HLH蛋白的HLH结构域介导的异源二聚化作用，通过阻止DNA结合，充当bHLH功能的天然显性负性抑制剂（Massari和Murre，2000年）。ID蛋白主要与E家族蛋白的成员相互作用，包括E12、E47、HEB和E2-2，但也与其他bHLH蛋白相互作用。ID蛋白促进细胞周期进程和细胞迁移，并限制细胞衰老以及包括少突胶质细胞在内的多种祖细胞类型的分化（Perk等人，2005年；Ling等人，2014年综述）。ID2和ID4的表达受EGR2:NAB2复合物的负性调控，该复合物被招募到启动子中的EGR结合位点。在发育过程中，ID2和ID4的抑制与EGR2:NAB2复合物在启动子区域结合的增加有关，这可能通过招募NURD染色质重塑复合物和组蛋白脱乙酰化酶来实现。研究表明，NAB2通过其保守的CHD4相互作用域（CID）与NURD复合物的CHD4和CHD3亚基相互作用（Mager等人，2008年；Srinivasan等人，2006年；Hung等人，2012年）。