The protein encoded by this gene belongs to theEGR family of Cys2His2-typezinc finger proteins. It is anuclear protein and functions as a transcriptional regulator. The products of target genes it activates are required for differentiation andmitogenesis. Studies suggest this is atumor suppressor gene.[5]
It has a distinct pattern of expression in the brain, and its induction has been shown to be associated with neuronal activity. Several studies suggest it has a role inneuronal plasticity.[6]
EGR-1 is an importanttranscription factor inmemory formation. It has an essential role inbrainneuronepigenetic reprogramming. EGR-1 recruits theTET1 protein that initiates a pathway ofDNA demethylation.[7] Removing DNA methylation marks allows the activation of downstream genes. EGR-1, together with TET1, is employed in programming the distribution of methylation sites on brain DNA during brain development, inlearning and in long-termneuronal plasticity. EGR-1 has also been found to regulate the expression ofVAMP2 (a protein important forsynapticexocytosis).[8]
Beside its function in the nervous system, there is significant evidence that EGR-1 along with its paralog EGR-2 is induced in fibrotic diseases has key functions in fibrinogenesis and is necessary for experimentally induced fibrosis in mice.[9]
The DNA-binding domain of EGR-1 consists of threezinc finger domains of the Cys2His2 type.The amino acid structure of the EGR-1 zinc finger domain is given in this table, using the single letter amino acid code. The fingers 1 to 3 are indicated by f1 - f3. The numbers are in reference to the residues (amino acids) ofalpha helix (there is no zero). The residues marked 'x' are not part of the zinc fingers, but rather serve to connect them all together.
Thecrystal structure ofDNA bound by the zinc finger domain of EGR-1 was solved in 1991, which greatly aided early research in zinc finger DNA-binding domains.[11]
The human EGR-1 protein contains (in its unprocessed form) 543 amino acids with a molecular weight of 57.5kDa, and the gene is located on thechromosome 5.
EGR-1 binds the DNA sequence 5'-GCG TGG GCG-3' (and similar ones like 5'-GCG GGG GCG-3').[12][13]The f1 position 6 binds the 5' G (the first base count from the left); the f1 position 3 to the second base (C); f1 position -1 binds to the third position (G); f2 position 6 to the fourth base (T); and so on.[14]
^Knapska E, Kaczmarek L (November 2004). "A gene for neuronal plasticity in the mammalian brain: Zif268/Egr-1/NGFI-A/Krox-24/TIS8/ZENK?".Progress in Neurobiology.74 (4):183–211.doi:10.1016/j.pneurobio.2004.05.007.PMID15556287.S2CID39251786.
^Sun Z, Xu X, He J, Murray A, Sun MA, Wei X, Wang X, McCoig E, Xie E, Jiang X, Li L, Zhu J, Chen J, Morozov A, Pickrell AM, Theus MH, Xie H. EGR1 recruits TET1 to shape the brain methylome during development and upon neuronal activity. Nat Commun. 2019 Aug 29;10(1):3892. doi: 10.1038/s41467-019-11905-3. PMID 31467272
^Pavletich NP, Pabo CO (May 1991). "Zinc finger-DNA recognition: crystal structure of a Zif268-DNA complex at 2.1 A".Science.252 (5007). New York, N.Y.:809–817.doi:10.1126/science.2028256.PMID2028256.S2CID38000717.
^Dreier B, Segal DJ, Barbas CF (November 2000). "Insights into the molecular recognition of the 5'-GNN-3' family of DNA sequences by zinc finger domains".Journal of Molecular Biology.303 (4):489–502.doi:10.1006/jmbi.2000.4133.PMID11054286.
Heath RG (March 1975). "Brain function and behavior. I. Emotion and sensory phenomena in psychotic patients and in experimental animals".The Journal of Nervous and Mental Disease.160 (3):159–175.doi:10.1097/00005053-197503000-00002.PMID1090709.S2CID23024944.
Adamson ED, Mercola D (2002). "Egr1 transcription factor: multiple roles in prostate tumor cell growth and survival".Tumour Biology.23 (2):93–102.doi:10.1159/000059711.PMID12065847.S2CID46795197.
Blaschke F, Bruemmer D, Law RE (August 2004). "Egr-1 is a major vascular pathogenic transcription factor in atherosclerosis and restenosis".Reviews in Endocrine & Metabolic Disorders.5 (3):249–254.doi:10.1023/B:REMD.0000032413.88756.ee.PMID15211096.S2CID11968305.
