NOBOX
| NOBOX | |||
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Gene ontology | |||
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| Sources:Amigo / QuickGO | |||
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| Location (UCSC) | Chr 7: 144.4 – 144.41 Mb | Chr 6: 43.28 – 43.29 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
| View/Edit Human | View/Edit Mouse |
Homeobox protein NOBOX, also known as newborn ovary homeobox protein, is a
Discovery
NOBOX is an in silico subtraction discovery when Suzumori et al. searched for novel genes involved in early mammalian folliculogenesis in 2002. It is one of the several genes that appeared in the search in expressed sequence tag (EST) databases of mouse.[6] It was then cloned and characterised for its genomic structure.
Gene location
The human NOBOX is located in chromosome 7q35 while the mouse NOBOX is in proximal chromosome 6.
Protein structure
The human NOBOX is a 14 kb protein and encoded by 8 exons.
Function
NOBOX is a homeobox gene that is preferentially expressed in oocytes. In mice, it is essential for folliculogenesis and regulation of oocyte-specific genes.[7] Regulation of these oocyte-specific genes is thru direct binding of NOBOX to its promoter regions via the specific consensus sequences, the NOBOX DNA binding elements (NBEs). There are three NBEs that have been identified: 5'-TAATTG-3', 5'-TAGTTG-3', and 5'-TAATTA-3'.[10] Knockout study of NOBOX against wild-type ovaries in newborn female mice revealed that 74% (28/38 genes) were downregulated more than 5-fold and 15% (5/33 genes) were upregulated more than 5-fold.[15] However, microRNA population is not affected by NOBOX in newborn ovaries. NOBOX also plays an important role in the suppression of male-determining genes such as Dmrt1.[15] Its deficiency can cause rapid loss of postnatal oocytes and during its absence in female mice, follicles are replaced by fibrous tissue.[6] Recently, a new role of NOBOX in controlling the G2/M arrest was discovered.[16]
Mutations and clinical significance
A mutation in the NOBOX gene is associated with
The POF syndrome is a highly heterogenous clinical disorder but a recent study showed the first homozygous mutation associated with NOBOX loss-of-function.[16] One patient out of 96 population diagnosed with POF in China was found with one novel homozygous truncating variant in the NOBOX gene. This truncated variant caused a defective transcriptional activation of GDF9, a well-known target of NOBOX, which led to the lost ability of NOBOX to induce G2/M arrest. This finding disagrees that mutation is a less common explanation for POF in Asian population.
Understanding the mutations in NOBOX homeodomain is important to researchers and clinicians to develop diagnostic and therapeutic approaches for POF such as genetic control of mammalian reproductive life-span, regulation of fertility, and generation of mature eggs in the lab.[8]
Interactions
References
- ^ a b c ENSG00000285328 GRCh38: Ensembl release 89: ENSG00000106410, ENSG00000285328 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000029736 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Entrez Gene: NOBOX oogenesis homeobox".
- ^ S2CID 7205659.
- ^ PMID 16597639.
- ^ S2CID 26646489.
- S2CID 10475561.
- ^ PMID 16997917.
- ^ S2CID 30861702.
- PMID 1742275.
- S2CID 24233895.
- S2CID 1678791.
- ^ PMID 17494914.
- ^ PMID 27836978.
- ^ PMID 17701902.
- PMID 9740426.
- ^ PMID 3960433.
- S2CID 19404756.
- PMID 25514101.
- S2CID 25656158.
- PMID 18930203.
- PMID 15950662.
- PMID 25790371.
- S2CID 16608843.
- PMID 28743298.
Further reading
- Rovescalli AC, Asoh S, Nirenberg M (October 1996). "Cloning and characterization of four murine homeobox genes". Proceedings of the National Academy of Sciences of the United States of America. 93 (20): 10691–6. PMID 8855241.
- Qin Y, Choi Y, Zhao H, Simpson JL, Chen ZJ, Rajkovic A (September 2007). "NOBOX homeobox mutation causes premature ovarian failure". American Journal of Human Genetics. 81 (3): 576–81. PMID 17701902.
- Brauner R, Bashamboo A, Rouget S, Goulet M, Philibert P, Sarda-Thibault H, Trivin C, Misrahi M, Sultan C, McElreavey K (June 2010). "Clinical, biological and genetic analysis of prepubertal isolated ovarian cyst in 11 girls". PLOS ONE. 5 (6): e11282. PMID 20593028.
- Zhao XX, Suzumori N, Yamaguchi M, Suzumori K (June 2005). "Mutational analysis of the homeobox region of the human NOBOX gene in Japanese women who exhibit premature ovarian failure". Fertility and Sterility. 83 (6): 1843–4. PMID 15950662.
- Oldenburg RA, van Dooren MF, de Graaf B, Simons E, Govaerts L, Swagemakers S, Verkerk JM, Oostra BA, Bertoli-Avella AM (December 2008). "A genome-wide linkage scan in a Dutch family identifies a premature ovarian failure susceptibility locus". Human Reproduction. 23 (12): 2835–41. PMID 18689850.
- van Dooren MF, Bertoli-Avellab AM, Oldenburg RA (August 2009). "Premature ovarian failure and gene polymorphisms". Current Opinion in Obstetrics & Gynecology. 21 (4): 313–7. S2CID 35641655.
- Rajkovic A, Pangas SA, Ballow D, Suzumori N, Matzuk MM (August 2004). "NOBOX deficiency disrupts early folliculogenesis and oocyte-specific gene expression". Science. 305 (5687): 1157–9. S2CID 26646489.
- Rossi E, Verri AP, Patricelli MG, Destefani V, Ricca I, Vetro A, Ciccone R, Giorda R, Toniolo D, Maraschio P, Zuffardi O (2008). "A 12Mb deletion at 7q33-q35 associated with autism spectrum disorders and primary amenorrhea". European Journal of Medical Genetics. 51 (6): 631–8. PMID 18675947.
- Qin Y, Shi Y, Zhao Y, Carson SA, Simpson JL, Chen ZJ (April 2009). "Mutation analysis of NOBOX homeodomain in Chinese women with premature ovarian failure". Fertility and Sterility. 91 (4 Suppl): 1507–9. PMID 18930203.