MITF gene expression

Stable Identifier
R-HSA-9730412
Type
Reaction [omitted]
Species
Homo sapiens
Compartment
nucleoplasm
ReviewStatus
5/5
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MITF gene expression
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MITF (Melanocyte inducing factor, also known as microphthalmia-associated transcription factor) is a key regulator of melanocyte biology. Melanocytes are specialized cells that contain melanosomes, organelles required for the synthesis of melanin (reviewed in Goding and Arnheiter, 2019). MITF is a critical determiner of melanocyte cell fate and controls expression of many of the genes involved in melanin biosynthesis, such as TYR, TYRP1 and DCT, as well as genes involved in cell adhesion and intracellular trafficking (which is required for melanosome transport, among other things) (Cheli et al, 2010; Ullrich et al, 1995; Chiaverini et al, 2008; Alves et al, 2017; Dilshat et al, 2021; reviewed in Goding and Arnheiter, 2019; Mort et al, 2015; White and Zon, 2008).
MITF expression is itself tightly regulated in a cell- and developmental stage specific manner. Melanocytes are derived from a multipotent precursor in the neural crest that can assume both a Schwann cell/glial cell fate and a melanocyte fate (reviewed in Mort et al, 2015; White and Zon, 2008). Cells destined to become melanocytes arise from neural crest cells along the entire vertebrate axis and migrate in the trunk region dorsolaterally from the neural crest through the dermis during development. Melanocytes can also arise from glial/Schwann cell precursors that migrate earlier in a ventral pattern. MITF expression is repressed in the multipotent precursor by a number of factors including SOX2, SOX9 and FOXD3 (Thomas and Erickson, 2009; Nitzan et al, 2013 a,b; Adameyko et al, 2012) and upregulated as cells undergo melanocyte fate determination through the action of transcription factors such as PAX3 and SOX10 (Bondurand et al, 2000; Potterf et al, 2000; reviewed in Goding and Arnheiter, 2019; Mort et al, 2015). Signaling through EDNRB and KIT are also required for melanocyte development and maintenance and for the expression of MITF (Aoki et al, 2005).
Literature References
PubMed ID Title Journal Year
25670789 The melanocyte lineage in development and disease

Mort, RL, Jackson, IJ, Patton, EE

Development 2015
34003523 Epigenetic regulation during melanocyte development and homeostasis

Dilshat, R, Vu, HN, Steingrímsson, E

Exp Dermatol 2021
18281284 Microphthalmia-associated transcription factor regulates RAB27A gene expression and controls melanosome transport

Chiaverini, C, Beuret, L, Flori, E, Busca, R, Abbe, P, Bille, K, Bahadoran, P, Ortonne, JP, Bertolotto, C, Ballotti, R

J Biol Chem 2008
22186729 Sox2 and Mitf cross-regulatory interactions consolidate progenitor and melanocyte lineages in the cranial neural crest

Adameyko, I, Lallemend, F, Furlan, A, Zinin, N, Aranda, S, Kitambi, SS, Blanchart, A, Favaro, R, Nicolis, S, Lübke, M, Müller, T, Birchmeier, C, Suter, U, Zaitoun, I, Takahashi, Y, Ernfors, P

Development 2012
27939378 MYO5A Gene Is a Target of MITF in Melanocytes

Alves, CP, Yokoyama, S, Goedert, L, Pontes, CLS, Sousa, JF, Fisher, DE, Espreafico, EM

J Invest Dermatol 2017
15768389 Cooperative and indispensable roles of endothelin 3 and KIT signalings in melanocyte development

Aoki, H, Motohashi, T, Yoshimura, N, Yamazaki, H, Yamane, T, Panthier, JJ, Kunisada, T

Dev Dyn 2005
23858437 Neural crest and Schwann cell progenitor-derived melanocytes are two spatially segregated populations similarly regulated by Foxd3

Nitzan, E, Pfaltzgraff, ER, Labosky, PA, Kalcheim, C

Proc Natl Acad Sci U S A 2013
23615280 A dynamic code of dorsal neural tube genes regulates the segregation between neurogenic and melanogenic neural crest cells

Nitzan, E, Krispin, S, Pfaltzgraff, ER, Klar, A, Labosky, PA, Kalcheim, C

Development 2013
10942418 Interaction among SOX10, PAX3 and MITF, three genes altered in Waardenburg syndrome

Bondurand, N, Pingault, V, Goerich, DE, Lemort, N, Sock, E, Le Caignec, C, Wegner, M, Goossens, M

Hum Mol Genet 2000
10982026 Transcription factor hierarchy in Waardenburg syndrome: regulation of MITF expression by SOX10 and PAX3

Potterf, SB, Furumura, M, Dunn, KJ, Arnheiter, H, Pavan, WJ

Hum Genet 2000
18786412 Melanocytes in development, regeneration, and cancer

White, RM, Zon, LI

Cell Stem Cell 2008
31123060 MITF-the first 25 years

Goding, CR, Arnheiter, H

Genes Dev 2019
19995375 Fifteen-year quest for microphthalmia-associated transcription factor target genes

Cheli, Y, Ohanna, M, Ballotti, R, Bertolotto, C

Pigment Cell Melanoma Res 2010
19403660 FOXD3 regulates the lineage switch between neural crest-derived glial cells and pigment cells by repressing MITF through a non-canonical mechanism

Thomas, AJ, Erickson, CA

Development 2009
26301891 MITF is a critical regulator of the carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) in malignant melanoma

Ullrich, N, Löffek, S, Horn, S, Ennen, M, Sánchez-Del-Campo, L, Zhao, F, Breitenbuecher, F, Davidson, I, Singer, BB, Schadendorf, D, Goding, CR, Helfrich, I

Pigment Cell Melanoma Res 2015
Participants
Input
Output
Participates
as an event of
This event is regulated
Negatively by
Regulator
PAX3:FOXD3 [nucleoplasm] (Homo sapiens)
Regulator
SOX2:MITF gene [nucleoplasm] (Homo sapiens)
Active Unit
SOX2 [nucleoplasm]
Regulator
AXL3:MITF gene [nucleoplasm] (Homo sapiens)
Active Unit
ALX3 [nucleoplasm]
Positively by
Regulator
LEF1:CTNNB1:MITF-M:MITF gene [nucleoplasm] (Homo sapiens)
Active Unit
LEF1;CTNNB1:MITF-M [nucleoplasm]
Regulator
EDN1, EDN3:EDNRB [plasma membrane] (Homo sapiens)
Regulator
p-S133-CREB1:MITF gene [nucleoplasm] (Homo sapiens)
Active Unit
p-S133-CREB1 [nucleoplasm]
Regulator
SOX10:PAX3:MITF gene [nucleoplasm] (Homo sapiens)
Active Unit
SOX10 [nucleoplasm]
PAX3 [nucleoplasm]
Authored
Rothfels, K  (2023-01-26)
Reviewed
Arnheiter, H  (2024-02-26)
de la Serna, IL  (2024-05-21)
Vu, HN  (2024-11-05)
Steingrímsson, E  (2024-11-05)
Created
Rothfels, K  (2021-05-07)
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