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- Table of Contents
Facts about Doublesex- and mab-3-related transcription factor 1.
Acts both as a transcription repressor and activator: prevents meiosis by restricting retinoic acid (RA)-dependent transcription and repressing STRA8 expression and promotes spermatogonial growth by activating spermatogonial differentiation genes, such as SOHLH1. Also plays a key role in postnatal sex care by keeping testis determination and preventing feminization: represses transcription of feminine promoting genes such as FOXL2 and activates male-specific genes.
Human | |
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Gene Name: | DMRT1 |
Uniprot: | Q9Y5R6 |
Entrez: | 1761 |
Belongs to: |
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DMRT family |
DM domain expressed in testis 1; DMT1DM domain expressed in testis protein 1; doublesex and mab-3 related transcription factor 1; doublesex- and mab-3-related transcription factor 1
Mass (kDA):
39.473 kDA
Human | |
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Location: | 9p24.3 |
Sequence: | 9; NC_000009.12 (841647..969090) |
Testis-specific. Expressed in prostate cancer (at protein level).
Nucleus.
This article will provide an overview of the DMRT1 marker, a gene that contributes to sex differentiation. This transcription factor is found in the gonads and is used in a number of biological assays. This article will help you understand the most effective ways to use this biomarker. You'll also learn how to apply boster bio to your experiments.
The sex differentiation mechanisms in vertebrates are complex and vary greatly between species. From complete genetic control to environmental cues, there is no single gene that drives sex determination in reptiles. However, DMRT1 is conserved among DM domain genes and has early embryonic expression that precedes the onset of gonadal sex differentiation. Furthermore, DMRT1 was found to induce expression in genetic female embryonic gonads.
To investigate the role of DMRT1 in the sex differentiation process, researchers used qPCR to quantify the number of 18S rRNA repeats in embryos and then normalize this copy number to the protein GAPDH. The resulting ratio is (18S/GAPDH), where higher DCt values indicate higher levels of 18S rRNA repeats. Using primers GAPDH and 5'-GGCTTTCCACAACTC-3', they amplified the gene in the same way as in the parental sex.
In the same manner as in wild-type chickens, the ZD+ZD embryos also had a similar pattern of markers in the cortical PGCs to the ZD+W controls. In contrast, the ZD-W embryos lacked both E2 synthesis and DMRT1 expression, and their early gonads were much smaller than those in the wild-type control animals. These findings suggest that DMRT1 may be required for proper allocation and proliferation of germ cells.
In medaka, a mutation in DMRT1 causes the reversal of sex. The resultant mutation is an embryo that fails to develop normally in a male-only fetus. When overexpressed in chicken embryos, Dmrt1 stimulates Amh and Sox9, which regulate the development of both male and female follicles.
DMRT1 is a conserved transcription factor that has an unusual DNA-binding motif (DM domain). This domain was first identified in the DOUBLESEX and MAB-3 transcription factors, which regulate mammalian sex differentiation. Recent studies have also implicated DMRT1 in the regulation of mammalian sex determination. Expression of DMRT1 is restricted to postnatal testis and developing gonads.
Dmrt1 has two regulatory regions: a somatic region and a distal region. The former directs gene expression to germ cells in the testis, while the latter receives transcription from a different promoter. Moreover, both regions contribute to the expression of Dmrt1 in germ cells and Sertoli cells. Consequently, DMRT1 is a crucial transcription factor for the maintenance of the germ line and self-directed postnatal differentiation.
In vitro studies revealed that a consensus binding site was identified for DMRT1 and reduced basal expression by fourfold in HEK293 cells. Furthermore, in mouse Sertoli cells, the binding site for DMRT1 inhibited transcription by up to 400 fold. Furthermore, DMRT1 was found to have an opposing expression pattern in the mouse ovary. Further, FOXL2 has been linked to the silencing of Dmrt1, suggesting that DMRT1 promoter is a crucial element for gene regulation.
In ovary cells, Dmrt1 promoter contains two regulatory regions: the somatic regulatory region, located between -3.2 kb and -2.8 kb, and the germ cell regulatory region, between -13 kb and 400 bps. Activation of Dmrt1 is inhibited by FOXL2, whereas silencing requires FOXL2 binding in granulosa cells occurs in XY and ZFPM2 somatic cells.
The DMRT1 marker is found in gonads. The gonads of genetic females show two distinct stages of development. Induction of genes for the male pathway is delayed by one day and normal expression by two stages. Infection with the DMRT1 gene results in localised masculinisation of the gonad. Nonetheless, overexpression of the gene in females does not have any overt effects.
Unlike vertebrates, which lack SRY, a single copy of DMRT1 is required for gonadal sex differentiation. Monotremes and non-mammals have no SRY gene, so other genes must be required. In addition, a second copy of the gene anti-Mullerian hormone has been identified in a Patagonian pejerrey (Odontesthes hatcheri) whose gonads carry a double copy of the male-specific Y chromosome. The rainbow trout, meanwhile, has an immune-related gene sdY in its gonads.
Another gene involved in the testis pathway is HEMGN. Hemogen, a Z-linked male factor, is involved in testicular differentiation. It has been shown that over-expression of HEMGN increases the levels of DMRT1 and SOX9. However, HEMGN and aromatase are down-regulated in the presence of DMRT1. This suggests that the DMRT1 marker may play an important role in regulating the expression of these genes in males.
The DMRT1 gene has been implicated as an essential regulator in gonadal differentiation in birds. It has been shown to inhibit the expression of the aromatase and female-type cortical development. Moreover, overexpression of DMRT1 suppresses the expression of hormones related to aromatase and cord-like structures. These findings indicate that DMRT1 is a key male sex marker in the male reproductive system.
DMRT1 is a highly expressed protein in eukaryotes. It is used in many biological assays, including the determination of transcription rates and DNA binding affinity. It is produced by a method called genome editing. The method involves editing the genome to create a specific gene variant, such as a loss-of-function mutation. This gene product has a 69 aa truncated size and lacks the predicted DNA binding domain.
DMRT1 expression is high in male and female germ cells. In fact, the absence of oocytes in ZD-W gonads may be the result of the perinatal failure of the germ cells to enter meiosis. Moreover, the absence of eggs in ZD+ZD birds is a proof of permanent sex reversal.
The DMRT1 gene is involved in male and female sexual development. It is a part of the sex chromosome, and has been considered an excellent candidate for the master SD gene. Interestingly, in some animals, there is a corrupted version of DMRT1 gene on the male chromosome. In this way, DMRT1 dosage has been shown in female ovaries. Its ZZ ovaries display typical female markers, and they also have clear evidence of follicular development.
DMRT1 is also found in some fish species. A mutant fish line containing dmrt1 and cyp19a1a has been registered at ZFIN as umo15. This mutant line is supposed to induce frameshift mutations and disrupt Dmrt1 protein synthesis. However, the dmrt1-/ fish line showed a female-biased phenotype. Interestingly, the mutant fish lines did not spawn, despite displaying normal spermatogenesis.
The DMRT1 gene is a conserved transcriptional regulator of male differentiation and testicular development in vertebrates. Mice lacking Dmrt1 develop teratomas while wild-type C57BL/6J mice do not. Mutant 129Sv germ cells undergo normal differentiation up to embryonic day 13.5, but fail to arrest mitos and express pluripotency markers. Several genes that regulate DMRT1 were identified by expression analysis. Missexpression of these genes may be responsible for teratoma development in DMRT1-/ mice.
The gene DMRT1 co-localizes with the 11-b-hydroxylase protein. Cells expressing sox5 co-localize with germ cells at different developmental stages. Sox5-positive cells also express vasa but do not express DMRT1bY. Therefore, DMRT1bY-positive cells are not germ cells. In adult ovary, very few cells are sox5-positive.
Interestingly, DMRT1 is a homolog of DM-W. Both proteins have the same molecular structure and are essential for germ cell development. The genetic link between DMRT1 and teratoma susceptibility is very sensitive to gene dosage and genetic background. Moreover, both genes act as dose-sensitive tumor suppressors, and natural variations in their activity are known to confer teratoma susceptibility.
DMRT1 has been implicated in premeiotic germ cell development. The protein plays a role in controlling entry to meiosis and the mitotic cell cycle. Dmrt1 antibody was used to confirm the null allele status of Dmrt1-/ testes. Further, it confirmed that the mutant testes did not produce Dmrt1 protein. Therefore, the mutation of Dmrt1 is a symptom of a defect in germ cell development.
XX reversal is another possible reason for DMRT1 expression in medaka. High temperature treatment causes XX sex reversal in medaka. The functional conservation of DMRT1 in medaka was also studied by Smith et al. There are currently no reports of a mutation in DMRT1 in humans. However, this gene is associated with DSD gonadal dysgenesis in the 46,XY, and YXY phenotypes.
PMID: 10332030 by Raymond C.S., et al. A region of human chromosome 9p required for testis development contains two genes related to known sexual regulators.
PMID: 10857744 by Calvari V., et al. A new submicroscopic deletion that refines the 9p region for sex reversal.
*More publications can be found for each product on its corresponding product page