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

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

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

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.
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.
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.
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.
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.

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[mattick-1] 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.

[yang-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.

[long-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.

[brennecke-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.

[oestreich-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.