Biology:FOXD3
 Generic protein structure example |
Forkhead box D3 also known as FOXD3 is a forkhead protein that in humans is encoded by the FOXD3 gene.[1]
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).[2]
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.[3] A recent finding further showed that Foxd3 is necessary as a repressor in the transition from ESC to epiblast-like cells (EpiLC).[4] 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.[5] 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.[6]
Neural Crest Cells
FOXD3 plays an important role in the development and differentiation of neural crest cells.[7] Specifically, it is thought that FOXD3 plays an important role in controlling the developmental switch between Schwann Cell Progenitors and Melanocytes.[7]
Clinical significance
Mutations in this gene cause vitiligo.[8]
References
- ↑ "Drosophila forkhead homologues are expressed in a lineage-restricted manner in human hematopoietic cells". Blood 81 (11): 2854–2859. June 1993. doi:10.1182/blood.V81.11.2854.2854. PMID 8499623.
- ↑ "FoxD3 and Grg4 physically interact to repress transcription and induce mesoderm in Xenopus". The Journal of Biological Chemistry 282 (4): 2548–2557. January 2007. doi:10.1074/jbc.M607412200. PMID 17138566.
- ↑ "Requirement for Foxd3 in maintaining pluripotent cells of the early mouse embryo". Genes & Development 16 (20): 2650–2661. October 2002. doi:10.1101/gad.1020502. PMID 12381664.
- ↑ "Foxd3 Promotes Exit from Naive Pluripotency through Enhancer Decommissioning and Inhibits Germline Specification". Cell Stem Cell 18 (1): 118–133. January 2016. doi:10.1016/j.stem.2015.09.010. PMID 26748758.
- ↑ "FOXD3 Regulates Pluripotent Stem Cell Potential by Simultaneously Initiating and Repressing Enhancer Activity". Cell Stem Cell 18 (1): 104–117. January 2016. doi:10.1016/j.stem.2015.10.003. PMID 26748757.
- ↑ "The paradox of Foxd3: how does it function in pluripotency and differentiation of embryonic stem cells?". Stem Cell Investigation 3: 73. 2016. doi:10.21037/sci.2016.09.20. PMID 27868055.
- ↑ 7.0 7.1 "Neural crest and Schwann cell progenitor-derived melanocytes are two spatially segregated populations similarly regulated by Foxd3". Proceedings of the National Academy of Sciences of the United States of America 110 (31): 12709–12714. July 2013. doi:10.1073/pnas.1306287110. PMID 23858437. Bibcode: 2013PNAS..11012709N.
- ↑ "Candidate functional promoter variant in the FOXD3 melanoblast developmental regulator gene in autosomal dominant vitiligo". The Journal of Investigative Dermatology 125 (2): 388–391. August 2005. doi:10.1111/j.0022-202X.2005.23822.x. PMID 16098053.
Further reading
- "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. March 2002. doi:10.1073/pnas.062041099. PMID 11891324. Bibcode: 2002PNAS...99.3663G.
- "Framingham Heart Study 100K Project: genome-wide associations for blood pressure and arterial stiffness". BMC Medical Genetics 8 (Suppl 1): S3. September 2007. doi:10.1186/1471-2350-8-S1-S3. PMID 17903302.
- "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. March 2001. doi:10.1086/318792. PMID 11179011.
- "YY1 and FoxD3 regulate antiretroviral zinc finger protein OTK18 promoter activation induced by HIV-1 infection". Journal of Neuroimmune Pharmacology 4 (1): 103–115. March 2009. doi:10.1007/s11481-008-9139-x. PMID 19034670.
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