ELF5 explained

E74-like factor 5 (ets domain transcription factor), is a gene found in both mice and humans.^[1] In humans it is also called ESE2.

Function

The protein encoded by this gene is a member of an epithelium-specific subclass of the ETS transcription factor family. In addition to its role in regulating the later stages of terminal differentiation of keratinocytes, it appears to regulate a number of epithelium-specific genes found in tissues containing glandular epithelium such as salivary gland and prostate. It has very low affinity to DNA due to its negative regulatory domain at the amino terminus. Two alternatively spliced transcript variants encoding different isoforms have been described for this gene.

Relevance to Disease

A role in breast or prostate cancer is known.^[2] There are preliminary reports that the C allele genetic variant of rs61882275 near chromosome location 11.13 with variable incidence in human populations^[3] is associated with severe COVID-19.^[4] Further investigation by others suggested the association was caused by a tissue-specific effect on ELF5 expression in lung endothelium by this allele which results in a more than 4-fold higher risk of severe COVID-19 in those with SARS-CoV2 infection.^[5]

Further reading

• Sharrocks AD, Brown AL, Ling Y, Yates PR . The ETS-domain transcription factor family . The International Journal of Biochemistry & Cell Biology . 29 . 12 . 1371–87 . Dec 1997 . 9570133 . 10.1016/S1357-2725(97)00086-1 .
• Zhou J, Ng AY, Tymms MJ, Jermiin LS, Seth AK, Thomas RS, Kola I . A novel transcription factor, ELF5, belongs to the ELF subfamily of ETS genes and maps to human chromosome 11p13-15, a region subject to LOH and rearrangement in human carcinoma cell lines . Oncogene . 17 . 21 . 2719–32 . Nov 1998 . 9840936 . 10.1038/sj.onc.1202198 . free .
• Oettgen P, Kas K, Dube A, Gu X, Grall F, Thamrongsak U, Akbarali Y, Finger E, Boltax J, Endress G, Munger K, Kunsch C, Libermann TA . Characterization of ESE-2, a novel ESE-1-related Ets transcription factor that is restricted to glandular epithelium and differentiated keratinocytes . The Journal of Biological Chemistry . 274 . 41 . 29439–52 . Oct 1999 . 10506207 . 10.1074/jbc.274.41.29439 . free .
• Lapinskas EJ, Palmer J, Ricardo S, Hertzog PJ, Hammacher A, Pritchard MA . A major site of expression of the ets transcription factor Elf5 is epithelia of exocrine glands . Histochemistry and Cell Biology . 122 . 6 . 521–6 . Dec 2004 . 15655699 . 10.1007/s00418-004-0713-x . 28936823 .
• Yaniw D, Hu J . Epithelium-specific ets transcription factor 2 upregulates cytokeratin 18 expression in pulmonary epithelial cells through an interaction with cytokeratin 18 intron 1 . Cell Research . 15 . 6 . 423–9 . Jun 2005 . 15987600 . 10.1038/sj.cr.7290310 . 4494830 .
• Tummala R, Sinha S . Differentiation-specific transcriptional regulation of the ESE-2 gene by a novel keratinocyte-restricted factor . Journal of Cellular Biochemistry . 97 . 4 . 766–81 . Mar 2006 . 16229011 . 10.1002/jcb.20685 . 46125527 .
• Choi YS, Sinha S . Determination of the consensus DNA-binding sequence and a transcriptional activation domain for ESE-2 . The Biochemical Journal . 398 . 3 . 497–507 . Sep 2006 . 16704374 . 1559455 . 10.1042/BJ20060375 .
• Lim J, Hao T, Shaw C, Patel AJ, Szabó G, Rual JF, Fisk CJ, Li N, Smolyar A, Hill DE, Barabási AL, Vidal M, Zoghbi HY . A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration . Cell . 125 . 4 . 801–14 . May 2006 . 16713569 . 10.1016/j.cell.2006.03.032 . 13709685 . free .

Notes and References

1. Web site: Entrez Gene: ELF5 E74-like factor 5 (ets domain transcription factor).
2. Piggin CL, Roden DL, Gallego-Ortega D, Lee HJ, Oakes SR, Ormandy CJ. ELF5 isoform expression is tissue-specific and significantly altered in cancer . Breast Cancer Research . 18 . 4 . 7 January 2016 . 1 . 10.1186/s13058-015-0666-0. 26738740 . 4704400 . free .
3. Web site: dbSNP Short Genetic Variations: rs61882275. January 21, 2022.
4. Kousathanas A, et al . 8 September 2021 . Whole genome sequencing identifies multiple loci for critical illness caused by COVID-19 . 10.1101/2021.09.02.21262965.
5. Pietzner M, et al . 19 January 2022 . ELF5 is a respiratory epithelial cell-specific risk gene for severe COVID-19 . 10.1101/2022.01.17.22269283.