ID1 and ID3 gene expression

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). ID1 and ID3 proteins also have established roles in hematopoiesis (Nogueira et al, 2000; Rivera and Murre, 2001; Hong et al, 2011; Zhao et al, 2016).
ID1 and ID3 gene expression is activated by the binding of CREB1 to CRE sites in the promoter. CREB recruits transcriptional co-activators p300 and CBP in a CREB S133 phosphorylation-dependent manner (reviewed in Shaywitz and Greenberg, 1999). ID1 and ID3 gene activation also depends on the CREB1-dependent recruitment of LYL1, a basic helix-loop-helix transcription factor with roles in cell proliferation and differentiation. The N-terminal domain of LYL1 interacts with the Q2 and KID domains of CREB1 in a manner that does not require CREB1 S133 phosphorylation (San Marina et al, 2008).

Literature References
PubMed ID Title Journal Year
21486943 ID1 and ID3 represent conserved negative regulators of human embryonic and induced pluripotent stem cell hematopoiesis

Bhatia, M, Hong, SH, Ji, J, Lee, JB, Lee, JH

J. Cell. Sci. 2011
18160048 Lyl1 interacts with CREB1 and alters expression of CREB1 target genes

San-Marina, S, Suarez Saiz, F, Trus, MR, Minden, MD, Han, Y

Biochim. Biophys. Acta 2008
27128622 Combined Id1 and Id3 Deletion Leads to Severe Erythropoietic Disturbances

Zhao, Q, Gonzalez, JP, Chang, C, Button, JL, Fraidenraich, D, Alzahrani, K

PLoS ONE 2016
10872467 CREB: a stimulus-induced transcription factor activated by a diverse array of extracellular signals

Greenberg, ME, Shaywitz, AJ

Annu. Rev. Biochem. 1999
11840323 The regulation and function of the Id proteins in lymphocyte development

Murre, C, Rivera, R

Oncogene 2001
11027551 Regulation of Id gene expression during embryonic stem cell-derived hematopoietic differentiation

Nogueira, MM, Vainchenker, W, Mitjavila-Garcia, MT, Filippi, MD, Sainteny, F, Le Pesteur, F, Dubart Kupperschmitt, A

Biochem. Biophys. Res. Commun. 2000
This event is regulated
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