Master regulator

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

History

The term "master regulator" was originally coined by geneticist Susumu Ohno in the late 1970s to refer to a hypothetical mechanism for sex determination. It has since been used to refer to a broader range of phenomena and its usage in the gene regulation literature has increased.[1]

Examples

Most genes considered master regulators code for transcription factor proteins, which in turn alter the expression of downstream genes in the pathway.[2] Canonical examples of master regulators include Oct-4 (also called POU5F1), SOX2, and NANOG, all transcription factors involved in maintaining pluripotency in stem cells.[2] Master regulators involved in development and morphogenesis can also appear as oncogenes relevant to tumorigenesis and metastasis, as with the Twist transcription factor.[3]

Other genes reported as master regulators code for SR proteins, which function as splicing factors,[4] and some noncoding RNAs.[5]

Criticism

The "master regulator" concept has been criticized for having an unclear definition[1] and for being a "simplified paradigm" that fails to account for the multifactorial influences on some cell fates.[6]

References

  1. 1 2 Chan, SS; Kyba, M (4 May 2013). "What is a Master Regulator?". Journal of stem cell research & therapy 3. PMID 23885309.
  2. 1 2 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 : TIG 26 (1): 21–8. PMID 19944475.
  3. ↑ 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. PMID 15210113.
  4. ↑ 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. PMID 19061484.
  5. ↑ 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.". Cell 128 (6): 1089–103. PMID 17346786.
  6. ↑ 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. PMID 23059426.
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