MITF-M-dependent IRF4 gene expression

Stable Identifier
R-HSA-9907147
Type
Reaction [omitted]
Species
Homo sapiens
Compartment
nucleoplasm, cytosol
ReviewStatus
5/5
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MITF-M-dependent IRF4 gene expression
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Interferon Regulatory Factor 4 (IRF4) is a winged-helix-turn-helix transcription factor that binds to interferon (IFN)-stimulated response elements in promoters of IFN-responsive genes. IRF4 is expressed in melanocytes, melanoma cell lines and in most melanomas and is associated with human pigmentation (Grossman et al, 1996; Sundram et al, 2003; Sulem et al, 2007; Han et al, 2008).
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). TFAPA2 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
18483556 A genome-wide association study identifies novel alleles associated with hair color and skin pigmentation

Han, J, Kraft, P, Nan, H, Guo, Q, Chen, C, Qureshi, A, Hankinson, SE, Hu, FB, Duffy, DL, Zhao, ZZ, Martin, NG, Montgomery, GW, Hayward, NK, Thomas, G, Hoover, RN, Chanock, S, Hunter, DJ

PLoS Genet 2008
17952075 Genetic determinants of hair, eye and skin pigmentation in Europeans

Sulem, P, Gudbjartsson, DF, Stacey, SN, Helgason, A, Rafnar, T, Magnusson, KP, Manolescu, A, Karason, A, Palsson, A, Thorleifsson, G, Jakobsdottir, M, Steinberg, S, Pálsson, S, Jonasson, F, Sigurgeirsson, B, Thorisdottir, K, Ragnarsson, R, Benediktsdottir, KR, Aben, KK, Kiemeney, LA, Olafsson, JH, Gulcher, J, Kong, A, Thorsteinsdottir, U, Stefansson, K

Nat. Genet. 2007
8921401 Cloning of human lymphocyte-specific interferon regulatory factor (hLSIRF/hIRF4) and mapping of the gene to 6p23-p25

Grossman, A, Mittrücker, HW, Nicholl, J, Suzuki, A, Chung, S, Antonio, L, Suggs, S, Sutherland, GR, Siderovski, DP, Mak, TW

Genomics 1996
12920225 Expression of the B-cell proliferation marker MUM1 by melanocytic lesions and comparison with S100, gp100 (HMB45), and MelanA

Sundram, U, Harvell, JD, Rouse, RV, Natkunam, Y

Mod Pathol 2003
Participants
Input
Output
Participates
as an event of
This event is regulated
Positively by
Regulator
MITF-M dimer:TFAP2A:IRF4 gene [nucleoplasm] (Homo sapiens)
Active Unit
MITF-M dimer [nucleoplasm]
TFAP2A homodimer [nucleoplasm]
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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