Master regulator gene

In genetics, a master regulator gene is a regulator gene at the top of a gene regulation hierarchy, particularly in regulatory pathways related to cell fate and differentiation.

Examples

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Most genes considered master regulators code for transcription factor proteins, which in turn alter the expression of downstream genes in the pathway.[1] Canonical examples of master regulators include Oct-4 (also called POU5F1), SOX2, and NANOG, all transcription factors involved in maintaining pluripotency in stem cells.[1] Master regulators involved in development and morphogenesis can also appear as oncogenes relevant to tumorigenesis and metastasis, as with the Twist transcription factor.[2]

Other genes reported as master regulators code for SR proteins, which function as splicing factors,[3] and some noncoding RNAs.[4]

Criticism

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The master regulator concept has been criticized for being a "simplified paradigm" that fails to account for the multifactorial influences on some cell fates.[5]

References

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  1. ^ a b Mattick, JS; Taft, RJ; Faulkner, GJ (January 2010). "A global view of genomic information--moving beyond the gene and the master regulator". Trends in Genetics. 26 (1): 21–8. doi:10.1016/j.tig.2009.11.002. PMID 19944475.
  2. ^ Yang, J; Mani, SA; Donaher, JL; Ramaswamy, S; Itzykson, RA; Come, C; Savagner, P; Gitelman, I; Richardson, A; Weinberg, RA (25 June 2004). "Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis". Cell. 117 (7): 927–39. doi:10.1016/j.cell.2004.06.006. PMID 15210113. S2CID 16181905.
  3. ^ Long, JC; Caceres, JF (1 January 2009). "The SR protein family of splicing factors: master regulators of gene expression". The Biochemical Journal. 417 (1): 15–27. doi:10.1042/BJ20081501. PMID 19061484.
  4. ^ Brennecke, J; Aravin, AA; Stark, A; Dus, M; Kellis, M; Sachidanandam, R; Hannon, GJ (23 March 2007). "Discrete small RNA-generating loci as master regulators of transposon activity in Drosophila" (PDF). Cell. 128 (6): 1089–103. doi:10.1016/j.cell.2007.01.043. PMID 17346786. S2CID 2246942.
  5. ^ Oestreich, KJ; Weinmann, AS (November 2012). "Master regulators or lineage-specifying? Changing views on CD4+ T cell transcription factors". Nature Reviews. Immunology. 12 (11): 799–804. doi:10.1038/nri3321. PMC 3584691. PMID 23059426.