Expression of ID2 and ID4 is repressed by EGR2:NAB

Stable Identifier
Reaction [BlackBoxEvent]
Homo sapiens
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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).

Literature References
PubMed ID Title Journal Year
25248477 Id proteins: small molecules, mighty regulators

Ling, F, Kang, B, Sun, XH

Curr. Top. Dev. Biol. 2014
16574654 NAB2 represses transcription by interacting with the CHD4 subunit of the nucleosome remodeling and deacetylase (NuRD) complex

Mager, GM, Ward, RM, Mayer, J, Svaren, J, Srinivasan, R

J. Biol. Chem. 2006
18456662 Active gene repression by the Egr2.NAB complex during peripheral nerve myelination

Wrabetz, L, Mager, GM, Ward, RM, Svaren, J, Jang, SW, Srinivasan, R

J. Biol. Chem. 2008
22302795 The nucleosome remodeling and deacetylase chromatin remodeling (NuRD) complex is required for peripheral nerve myelination

Hung, H, Svaren, J, Kohnken, R

J. Neurosci. 2012
10611221 Helix-loop-helix proteins: regulators of transcription in eucaryotic organisms

Murre, C, Massari, ME

Mol. Cell. Biol. 2000
16034366 Id family of helix-loop-helix proteins in cancer

Benezra, R, Iavarone, A, Perk, J

Nat. Rev. Cancer 2005
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