FOXD3 binds PAX3

Stable Identifier
R-HSA-9732097
Type
Reaction [binding]
Species
Homo sapiens
Compartment
nucleoplasm
ReviewStatus
5/5
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FOXD3 binds PAX3
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FOXD3 is a transcription factor with a role in specifying cell fates in the neural crest (reviewed in Mort et al, 2015; Golson and Kaestner, 2016; Goding and Arnheiter, 2019). In a bipotent precursor that can give rise to both glial and melanocyte cell lineages, FOXD3 represses expression of microphthalmia-associated transcription factor (MITF), itself a key regulator of melanocyte cell fate (reviewed in Goding and Arnheiter, 2019).
FOXD3 contains DNA-binding motifs and can act as either a transcriptional activator or a transcriptional repressor in different contexts by direct binding to a cognate DNA element 5'-A[AT]T[AG]TTTGTTT-3' (Guo et al, 2002; reviewed in Mort et al, 2015). Consistent with this, in zebrafish models, FOXD3 has been demonstrated to bind directly to the promoter of the equivalent of MITF-M (in zebrafish called mitfa) and repress expression in the bipotent precursor and non-melanocytic lineages (Curran et al, 2009, Curran et al, 2010).
In contrast, direct binding of FOXD3 was not observed by electrophoretic mobility shift assays using nuclear extracts from B16-F10 mouse melanoma cells. Instead, in this system, FOXD3 appears to repress MITF gene expression by directly binding to the MITF-transcriptional activator PAX3 and inhibiting its interaction with PAX3 sites in the MITF-M promoter. Consistent with this, chicken GST-FOXD3 interacts directly with PAX3 as assessed with a pulldown assay with B16-F10 nuclear extract (Thomas and Erickson, 2009).
Literature References
PubMed ID Title Journal Year
19403660 FOXD3 regulates the lineage switch between neural crest-derived glial cells and pigment cells by repressing MITF through a non-canonical mechanism

Erickson, CA, Thomas, AJ

Development 2009
20460180 Interplay between Foxd3 and Mitf regulates cell fate plasticity in the zebrafish neural crest

Prendergast, A, Raible, DW, Parichy, DM, Kunkel, GR, Lister, JA, Curran, K

Dev Biol 2010
27965437 Fox transcription factors: from development to disease

Kaestner, KH, Golson, ML

Development 2016
19527705 Foxd3 controls melanophore specification in the zebrafish neural crest by regulation of Mitf

Raible, DW, Lister, JA, Curran, K

Dev Biol 2009
31123060 MITF-the first 25 years

Arnheiter, H, Goding, CR

Genes Dev 2019
11891324 The embryonic stem cell transcription factors Oct-4 and FoxD3 interact to regulate endodermal-specific promoter expression

Guo, Y, Reinbold, R, Ramsey, H, Robertson, K, Kelley, M, Scholer, H, Costa, R, Vance, G, Hromas, R, Starnes, T

Proc Natl Acad Sci U S A 2002
25670789 The melanocyte lineage in development and disease

Jackson, IJ, Patton, EE, Mort, RL

Development 2015
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FOXD3 binds PAX3 (Gallus gallus)
Authored
Rothfels, K  (2023-01-26)
Reviewed
de la Serna, IL  (2024-05-21)
Arnheiter, H  (2024-02-26)
Created
Rothfels, K  (2021-05-26)
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