FOXD3

FOXD3
Identifiers
Aliases	FOXD3, AIS1, Genesis, HFH2, VAMAS2, forkhead box D3
External IDs	OMIM: 611539; MGI: 1347473; HomoloGene: 49239; GeneCards: FOXD3; OMA:FOXD3 - orthologs
Gene location (Human) Chr. Chromosome 1 (human) Band 1p31.3 Start 63,322,567 bp End 63,325,128 bp
Gene location (Mouse) Chr. Chromosome 4 (mouse) Band 4 C6|4 45.71 cM Start 99,544,536 bp End 99,546,859 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in sural nerve spinal ganglia trigeminal ganglion muscle layer of sigmoid colon gastric mucosa right auricle seminal vesicula left coronary artery transverse colon olfactory zone of nasal mucosa Top expressed in neural crest epiblast spinal cord urethra ureter neural groove neural fold salivary gland embryo spinal ganglia More reference expression data BioGPS n/a
Gene ontology Molecular function protein binding DNA-binding transcription repressor activity, RNA polymerase II-specific sequence-specific DNA binding RNA polymerase II transcription regulatory region sequence-specific DNA binding DNA-binding transcription factor activity DNA binding DNA-binding transcription factor activity, RNA polymerase II-specific Cellular component nucleoplasm nucleus Biological process negative regulation of transcription by RNA polymerase II positive regulation of transcription by RNA polymerase II regulation of transcription, DNA-templated multicellular organism development somatic stem cell population maintenance in utero embryonic development transcription, DNA-templated anatomical structure morphogenesis cell differentiation regulation of transcription by RNA polymerase II Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 27022 15221 Ensembl ENSG00000187140 ENSMUSG00000067261 UniProt Q9UJU5 Q61060 RefSeq (mRNA) NM_012183 NM_010425 RefSeq (protein) NP_036315 NP_034555 Location (UCSC) Chr 1: 63.32 – 63.33 Mb Chr 4: 99.54 – 99.55 Mb PubMed search
Wikidata
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Forkhead box D3 also known as FOXD3 is a forkhead protein that in humans is encoded by the FOXD3 gene.

Function

This gene belongs to the forkhead protein family of transcription factors which is characterized by a DNA-binding forkhead domain. FoxD3 functions as a transcriptional repressor and contains the C-terminal engrailed homology-1 motif (eh1), which provides an interactive surface with a transcriptional co-repressor Grg4 (Groucho-related gene-4).

Stem Cells

Multiple studies have suggested Foxd3 involvement in the transition from naive to primed pluripotent stem cells in embryo development. Previously, Foxd3 was demonstrated to be required in maintaining pluripotency in mouse embryonic stem cells. A recent finding further showed that Foxd3 is necessary as a repressor in the transition from ESC to epiblast-like cells (EpiLC). The study proposed that Foxd3 is associated with inactivation of important naive pluripotency genes by its modification of chromatin structures via recruiting histone demethylases and decreasing the number of activating factors. Another proposed mechanism on the other hand argued that Foxd3 begins nucleosome removal and induction to a "primed" pluripotent state by recruiting Brg1, a nucleosome remodeler, and then acts as a repressor of maximal activation of those enhancers by recruiting histone deacetylases, suggesting a complex mediating function in which enhancers are primed for some future controlled time-point rather than immediate expression. While there is no ambiguity that Foxd3 plays an important role regulating the transition from naive to primed pluripotency state, the two models show a different process. Attempts to reconcile the conclusions of the two studies have further suggested that Foxd3 functions as all of the above.

Neural Crest Cells

FOXD3 plays an important role in the development and differentiation of neural crest cells. Specifically, it is thought that FOXD3 plays an important role in controlling the developmental switch between Schwann Cell Progenitors and Melanocytes.

Clinical significance

Mutations in this gene cause vitiligo.

Further reading

• Guo Y, Costa R, Ramsey H, Starnes T, Vance G, Robertson K, et al. (March 2002). "The embryonic stem cell transcription factors Oct-4 and FoxD3 interact to regulate endodermal-specific promoter expression". Proceedings of the National Academy of Sciences of the United States of America. 99 (6): 3663–3667. Bibcode:2002PNAS...99.3663G. doi:10.1073/pnas.062041099. PMC 122580. PMID 11891324.
• Levy D, Larson MG, Benjamin EJ, Newton-Cheh C, Wang TJ, Hwang SJ, et al. (September 2007). "Framingham Heart Study 100K Project: genome-wide associations for blood pressure and arterial stiffness". BMC Medical Genetics. 8 (Suppl 1): S3. doi:10.1186/1471-2350-8-S1-S3. PMC 1995621. PMID 17903302.
• Saleem RA, Banerjee-Basu S, Berry FB, Baxevanis AD, Walter MA (March 2001). "Analyses of the effects that disease-causing missense mutations have on the structure and function of the winged-helix protein FOXC1". American Journal of Human Genetics. 68 (3): 627–641. doi:10.1086/318792. PMC 1274476. PMID 11179011.
• Buescher JL, Martinez LB, Sato S, Okuyama S, Ikezu T (March 2009). "YY1 and FoxD3 regulate antiretroviral zinc finger protein OTK18 promoter activation induced by HIV-1 infection". Journal of Neuroimmune Pharmacology. 4 (1): 103–115. doi:10.1007/s11481-008-9139-x. PMC 2680142. PMID 19034670.