MITF-M dimer and TFAP2A bind intronic elements in the IRF4 gene

Stable Identifier
R-HSA-9907144
Type
Reaction [binding]
Species
Homo sapiens
Compartment
nucleoplasm
ReviewStatus
5/5
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MITF-M dimer and TFAP2A bind intronic elements in the IRF4 gene
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Expression of IRF4 in melanoma cells and in zebrafish is regulated by the binding of MITF-M and TFAP2A to cognate binding sites located in intron 4, as assessed by ChIP, EMSA and reporter gene assay (Kenny et al, 2005; Praetorius et al, 2013). Studies in murine melanocytes and in mouse support a role for IRF4 in mouse pigmentation in a manner that depends on MITF (Praetorius et al, 2013).
Consistent with a role for TFAP2A in promoting IRF4 expression, a naturally occurring SNP in intron 4 of IRF4 that impairs binding of TFAP2A to its site decreases expression of IRF4 (Praetorius et al, 2013). TFAP2A and TFAP2C, the two TFAP family members with the highest expression in melanocytes, appear to work cooperatively with MITF to activate a subset of target genes involved in proliferation and pigmentation. TFAP family members may act as 'pioneer' transcription factors for MITF, increasing MITF binding and chromatin accessibility (Kenny et al, 2022).
Literature References
PubMed ID Title Journal Year
35580127 TFAP2 paralogs facilitate chromatin access for MITF at pigmentation and cell proliferation genes

Kenny, C, Dilshat, R, Seberg, HE, Van Otterloo, E, Bonde, G, Helverson, A, Franke, CM, Steingrímsson, E, Cornell, RA

PLoS Genet 2022
24267888 A polymorphism in IRF4 affects human pigmentation through a tyrosinase-dependent MITF/TFAP2A pathway

Praetorius, C, Grill, C, Stacey, SN, Metcalf, AM, Gorkin, DU, Robinson, KC, Van Otterloo, E, Kim, RS, Bergsteinsdóttir, K, Ogmundsdóttir, MH, Magnusdottir, E, Mishra, PJ, Davis, SR, Guo, T, Zaidi, MR, Helgason, AS, Sigurdsson, MI, Meltzer, PS, Merlino, G, Petit, V, Larue, L, Loftus, SK, Adams, DR, Sobhiafshar, U, Emre, NC, Pavan, WJ, Cornell, R, Smith, AG, Mccallion, AS, Fisher, DE, Stefansson, K, Sturm, RA, Steingrímsson, E

Cell 2013
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Authored
Rothfels, K  (2024-03-01)
Reviewed
de la Serna, IL  (2024-05-21)
Vu, HN  (2024-11-05)
Steingrímsson, E  (2024-11-05)
Created
Rothfels, K  (2024-04-04)
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