Biology:EGR2

From HandWiki

Early growth response protein 2 (EGR2), also known as Krox20, is a transcription factor encoded by the EGR2 gene in humans. It is highly expressed in migrating neural crest cells and later in neural crest-derived cells of the cranial ganglia.[1][2][3] Expression of EGR2 is restricted to early hindbrain development,[2][4] and the gene is evolutionarily conserved among vertebrates, including humans, mice, chicks, and zebrafish.[5] The conservation of its amino acid sequence and embryonic expression pattern underscores its essential role in hindbrain segmentation and neural differentiation.[3][6][7][8]

Structure

The EGR2 protein contains three tandem C2H2-type zinc finger domains that mediate specific DNA binding.[2][4] These zinc fingers enable EGR2 to function as a transcriptional regulator of genes involved in neural development and myelination.

Function

EGR2 acts as a transcription factor that regulates gene expression during neural development and peripheral nerve myelination. It binds to specific DNA sequences via its zinc finger motifs to control target genes essential for Schwann cell differentiation and myelin sheath formation.[9] It is also expressed in osteoprogenitor cells and has been implicated in the proliferation of Ewing sarcoma–derived cell lines, suggesting a role in both bone biology and tumorigenesis.[10][11]

Clinical significance

Mutations in EGR2 are associated with several hereditary demyelinating neuropathies, including Charcot–Marie–Tooth disease type 1D,[9] Dejerine–Sottas disease,[12] and congenital hypomyelinating neuropathy.[13] Recent studies have also suggested that EGR2 expression in hair follicle stem cells may influence hair maintenance and pigmentation, with loss of Krox20-expressing cells contributing to male-pattern baldness and graying hair.[14]

Deletion of Egr2 in mice results in loss of protein-coding capacity, including the DNA-binding domain, leading to perinatal lethality and severe hindbrain malformations.[2][4] These defects include aberrant formation of cranial sensory ganglia, fusion of the trigeminal (V), facial (VII), and auditory (VIII) nerves, and disorganization of their proximal roots as they enter the brainstem.[15][16][17]

References

  1. ↑ "Structure, chromosome location, and expression of the mouse zinc finger gene Krox-20: multiple gene products and coregulation with the proto-oncogene c-fos". Molecular and Cellular Biology 9 (2): 787–97. February 1989. doi:10.1128/mcb.9.2.787. PMID 2496302. 
  2. ↑ 2.0 2.1 2.2 2.3 "Perinatal lethality and defects in hindbrain development in mice homozygous for a targeted mutation of the zinc finger gene Krox20". Genes & Development 7 (11): 2071–84. November 1993. doi:10.1101/gad.7.11.2071. PMID 8224839. 
  3. ↑ 3.0 3.1 "Segment-specific expression of a zinc-finger gene in the developing nervous system of the mouse". Nature 337 (6206): 461–4. February 1989. doi:10.1038/337461a0. PMID 2915691. Bibcode: 1989Natur.337..461W. 
  4. ↑ 4.0 4.1 4.2 "The structure and expression of the Xenopus Krox-20 gene: conserved and divergent patterns of expression in rhombomeres and neural crest". Mechanisms of Development 40 (1–2): 73–84. January 1993. doi:10.1016/0925-4773(93)90089-g. PMID 8443108. 
  5. ↑ "Activation of the zinc finger encoding gene krox-20 in adult rat brain: comparison with zif268". Brain Research. Molecular Brain Research 13 (3): 263–6. April 1992. doi:10.1016/0169-328x(92)90034-9. PMID 1317498. 
  6. ↑ "Segmental expression of Hox-2 homoeobox-containing genes in the developing mouse hindbrain". Nature 341 (6241): 405–9. October 1989. doi:10.1038/341405a0. PMID 2571936. Bibcode: 1989Natur.341..405W. 
  7. ↑ "A distinct Hox code for the branchial region of the vertebrate head". Nature 353 (6347): 861–4. October 1991. doi:10.1038/353861a0. PMID 1682814. Bibcode: 1991Natur.353..861H. 
  8. ↑ "Cloning of the zebrafish krox-20 gene (krx-20) and its expression during hindbrain development". Nucleic Acids Research 21 (5): 1087–95. March 1993. doi:10.1093/nar/21.5.1087. PMID 8464695. 
  9. ↑ 9.0 9.1 "Entrez Gene: EGR2 early growth response 2 (Krox-20 homolog, Drosophila)". https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=1959. 
  10. ↑ "Epidermal growth factor receptor (EGFR) signaling promotes proliferation and survival in osteoprogenitors by increasing early growth response 2 (EGR2) expression" (in en). The Journal of Biological Chemistry 288 (28): 20488–98. July 2013. doi:10.1074/jbc.M112.447250. PMID 23720781. 
  11. ↑ "Chimeric EWSR1-FLI1 regulates the Ewing sarcoma susceptibility gene EGR2 via a GGAA microsatellite". Nature Genetics 47 (9): 1073–8. September 2015. doi:10.1038/ng.3363. PMID 26214589. 
  12. ↑ "EGR2 mutation R359W causes a spectrum of Dejerine-Sottas neuropathy". Neurogenetics 3 (3): 153–7. July 2001. doi:10.1007/s100480100107. PMID 11523566. 
  13. ↑ "Mutations in the early growth response 2 (EGR2) gene are associated with hereditary myelinopathies". Nature Genetics 18 (4): 382–4. April 1998. doi:10.1038/ng0498-382. PMID 9537424. 
  14. ↑ "Scientists find skin cells at the root of balding, gray hair". http://www.utsouthwestern.edu/newsroom/news-releases/year-2017/may/gray-hair.html. 
  15. ↑ "Isolation of the mouse Hox-2.9 gene; analysis of embryonic expression suggests that positional information along the anterior-posterior axis is specified by mesoderm". Development 110 (2): 589–607. October 1990. doi:10.1242/dev.110.2.589. PMID 1983472. 
  16. ↑ "Segment-specific expression of a homoeobox-containing gene in the mouse hindbrain". Nature 341 (6238): 156–9. September 1989. doi:10.1038/341156a0. PMID 2571087. Bibcode: 1989Natur.341..156M. 
  17. ↑ "Conserved segmental expression of Krox-20 in the vertebrate hindbrain and its relationship to lineage restriction". Development Suppl 2: 59–62. 1991. doi:10.1242/dev.113.Supplement_2.59. PMID 1688180. 

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.



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