scholarly journals The Sex-Determining Factors SRY and SOX9 Regulate Similar Target Genes and Promote Testis Cord Formation during Testicular Differentiation

Cell Reports ◽  
2014 ◽  
Vol 8 (3) ◽  
pp. 723-733 ◽  
Author(s):  
Yunmin Li ◽  
Ming Zheng ◽  
Yun-Fai Chris Lau
Keyword(s):  
Target Genes ◽  
Determining Factors ◽  
Testicular Differentiation ◽  
Testis Cord

scholarly journals Doublesex- and Mab-3-Related Transcription Factor-1 Repression of Aromatase Transcription, a Possible Mechanism Favoring the Male Pathway in Tilapia

Endocrinology ◽  
2010 ◽  
Vol 151 (3) ◽  
pp. 1331-1340 ◽  
Author(s):  
De-Shou Wang ◽  
Lin-Yan Zhou ◽  
Tohru Kobayashi ◽  
Masaru Matsuda ◽  
Yasushi Shibata ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Target Genes ◽  
Hek 293 ◽  
Aromatase Gene ◽  
Estrogen Production ◽  
Testicular Differentiation ◽  
Related Transcription Factor ◽  
Transcription Factor 1

Doublesex- and Mab-3-related transcription factor-1 (Dmrt1) is an important transcription factor implicated in early testicular differentiation in vertebrates, but its target genes are largely unknown. In the Nile tilapia, estrogen is the natural inducer of ovarian differentiation. Our recent studies have shown that Forkhead-l2 up-regulated transcription of the Cyp19a1a gene (aromatase) in the gonads in a female-specific manner. However, the upstream factor(s) down-regulating Cyp19a1a expression during testicular differentiation remains unclear. In the present study, we used in vitro (promoter analysis) and in vivo (transgenesis and in situ hybridization) approaches to examine whether Dmrt1 inhibits Cyp19a1a’s transcriptional activity. The in vitro analysis using luciferase assays revealed that Dmrt1 repressed basal as well as Ad4BP/SF-1-activated Cyp19a1a transcription in HEK 293 cells. Luciferase assays with various deletions of Dmrt1 also showed that the Doublesex and Mab-3 domain is essential for the repression. In vitro-translated Dmrt1 and the nuclear extract from tilapia testis could directly bind to the palindrome sequence ACATATGT in the Cyp19a1a promoter, as determined by EMSAs. Transgenic overexpression of Dmrt1 in XX fish resulted in decreased aromatase gene expression, reduced serum estradiol-17β levels, retardation of the ovarian cavity’s development, varying degrees of follicular degeneration, and even a partial to complete sex reversal. Our results indicate that aromatase is one of the targets of Dmrt1. Dmrt1 suppresses the female pathway by repressing aromatase gene transcription and estrogen production in the gonads of tilapia and possibly other vertebrates.

scholarly journals CREB Promotes Beta Cell Gene Expression by Targeting Its Coactivators to Tissue-Specific Enhancers

2019 ◽  
Vol 39 (17) ◽  
Author(s):  
Sam Van de Velde ◽  
Ezra Wiater ◽  
Melissa Tran ◽  
Yousang Hwang ◽  
Philip A. Cole ◽  
...  
Keyword(s):  
Gene Expression ◽  
Beta Cell ◽  
Rna Polymerase Ii ◽  
Target Genes ◽  
Cell Function ◽  
Pancreatic Beta Cell ◽  
Specific Gene ◽  
Distal Enhancer ◽  
Determining Factors ◽  
Cell Gene Expression

ABSTRACT CREB mediates effects of cyclic AMP on cellular gene expression. Ubiquitous CREB target genes are induced following recruitment of CREB and its coactivators to promoter proximal binding sites. We found that CREB stimulates the expression of pancreatic beta cell-specific genes by targeting CBP/p300 to promoter-distal enhancer regions. Subsequent increases in histone acetylation facilitate recruitment of the coactivators CRTC2 and BRD4, leading to release of RNA polymerase II over the target gene body. Indeed, CREB-induced hyperacetylation of chromatin over superenhancers promoted beta cell-restricted gene expression, which is sensitive to inhibitors of CBP/p300 and BRD4 activity. Neurod1 appears critical in establishing nucleosome-free regions for recruitment of CREB to beta cell-specific enhancers. Deletion of a CREB-Neurod1-bound enhancer within the Lrrc10b-Syt7 superenhancer disrupted the expression of both genes and decreased beta cell function. Our results demonstrate how cross talk between signal-dependent and lineage-determining factors promotes the expression of cell-type-specific gene programs in response to extracellular cues.

scholarly journals FGF9, activin and TGFβ promote testicular characteristics in an XX gonad organ culture model

Reproduction ◽  
2016 ◽  
Vol 152 (5) ◽  
pp. 529-543 ◽  
Author(s):  
Sonja E Gustin ◽  
Jessica M Stringer ◽  
Kirsten Hogg ◽  
Andrew H Sinclair ◽  
Patrick S Western
Keyword(s):  
Growth Factors ◽  
Germ Line ◽  
Supporting Cell ◽  
Testicular Development ◽  
Male Germ Line ◽  
Testis Development ◽  
Culture Model ◽  
Determining Factors ◽  
Testis Cord

Testis development is dependent on the key sex-determining factors SRY and SOX9, which activate the essential ligand FGF9. Although FGF9 plays a central role in testis development, it is unable to induce testis formation on its own. However, other growth factors, including activins and TGFβs, also present testis during testis formation. In this study, we investigated the potential of FGF9 combined with activin and TGFβ to induce testis development in cultured XX gonads. Our data demonstrated differing individual and combined abilities of FGF9, activin and TGFβ to promote supporting cell proliferation, Sertoli cell development and male germ line differentiation in cultured XX gonads. FGF9 promoted proliferation of supporting cells in XX foetal gonads at rates similar to those observed in vivo during testis cord formation in XY gonads but was insufficient to initiate testis development. However, when FGF9, activin and TGFβ were combined, aspects of testicular development were induced, including the expression of Sox9, morphological reorganisation of the gonad and deposition of laminin around germ cells. Enhancing β-catenin activity diminished the testis-promoting activities of the combined growth factors. The male promoting activity of FGF9 and the combined growth factors directly or indirectly extended to the germ line, in which a mixed phenotype was observed. FGF9 and the combined growth factors promoted male germ line development, including mitotic arrest, but expression of pluripotency genes was maintained, rather than being repressed. Together, our data provide evidence that combined signalling by FGF9, activin and TGFβ can induce testicular characteristics in XX gonads.

The molecular genetics of Sry and its role in mammalian sex determination

1995 ◽  
Vol 350 (1333) ◽  
pp. 205-214 ◽  
Keyword(s):  
Sex Determination ◽  
Target Genes ◽  
Gene Action ◽  
Human Gene ◽  
Cell Lineage ◽  
Supporting Cell ◽  
Gonadal Development ◽  
Genital Ridge ◽  
Testis Differentiation ◽  
Testicular Differentiation

The process of sex determination, by which is meant the decision as to whether an embryo develops as a male or a female, is considered as a paradigm of how gene action can influence developmental fate. In mammals the decision is dependent on the action of the testis determining gene present on the Y chromosome, now known to be the gene Sry . Sry is expressed for only a brief period in the mouse embryo and must act to initiate rather than maintain the pathway of gene activity required for testis differentiation. It probably acts within cells of the supporting cell lineage to direct their differentiation into Sertoli cells, rather than the granulosa cells characteristic of the ovary. Other lineages in the gonad then follow the male pathway. The nature of the Sry transcript in the genital ridge of mice has been determined and compared with that from the human gene which is dramatically different. The expression of Sry has been carefully examined during the critical stages of genital ridge development and compared to the expression of a number of other genes involved in gonadal development and male development such as that for anti-Mullerian hormone. This has defined the period in which Sry must act to between 11 and 11.5 days post coitum . The expression of Sry has also been examined in cases of sex reversal in the mouse. There is a dependence on level of expression and extent of testicular differentiation that suggests thresholds for both the amount of SRY per cell and the number of cells expressing the gene. The SRY protein interacts with DNA through an HMG box type of DNA binding domain, however at present no definite target genes have been found. Progress on strategies to find such genes is discussed.

Nuclear receptors in disease: the oestrogen receptors

2004 ◽  
Vol 40 ◽  
pp. 157-167 ◽  
Author(s):  
Maria Nilsson ◽  
Karin Dahlman-Wright ◽  
Jan-Åke Gustafsson
Keyword(s):  
Nuclear Receptors ◽  
Target Genes ◽  
Receptor Subtype ◽  
Target Tissue ◽  
Oestrogen Receptors ◽  
Nucleotide Polymorphisms ◽  
Cell Type ◽  
Single Nucleotide ◽  
Beneficial Effects ◽  
The Family

For several decades, it has been known that oestrogens are essential for human health. The discovery that there are two oestrogen receptors (ERs), ERalpha and ERbeta, has facilitated our understanding of how the hormone exerts its physiological effects. The ERs belong to the family of ligand-activated nuclear receptors, which act by modulating the expression of target genes. Studies of ER-knockout (ERKO) mice have been instrumental in defining the relevance of a given receptor subtype in a certain tissue. Phenotypes displayed by ERKO mice suggest diseases in which dysfunctional ERs might be involved in aetiology and pathology. Association between single-nucleotide polymorphisms (SNPs) in ER genes and disease have been demonstrated in several cases. Selective ER modulators (SERMs), which are selective with regard to their effects in a certain cell type, already exist. Since oestrogen has effects in many tissues, the goal with a SERM is to provide beneficial effects in one target tissue while avoiding side effects in others. Refined SERMs will, in the future, provide improved therapeutic strategies for existing and novel indications.

381: Promoter Hypermethylation Profile of Kidney Cancer with New Pro-Apoptotic P53 Target Genes and Possible Clinical Implications

2006 ◽  
Vol 175 (4S) ◽  
pp. 125-125
Author(s):  
Frank Christoph ◽  
Steffen Weikert ◽  
Carsten Kempkensteffen ◽  
Martin Schostak ◽  
Hans Krause ◽  
...  
Keyword(s):  
Kidney Cancer ◽  
Target Genes ◽  
Promoter Hypermethylation ◽  
Clinical Implications ◽  
P53 Target Genes

Analysis of the antiviral efficacy and target genes of the Lambda-interferons IL-28A and IL-29

2010 ◽  
Vol 48 (08) ◽  
Author(s):  
J Diegelmann ◽  
CJ Auernhammer ◽  
B Göke ◽  
H Diepolder ◽  
S Brand
Keyword(s):  
Target Genes ◽  
Antiviral Efficacy

FGF-2 and TIMP-3 are the target genes of β-catenin in thyroid carcinomas

2004 ◽  
Vol 112 (S 1) ◽  
Author(s):  
N Kremenevskaja ◽  
J Lauber ◽  
J Buer ◽  
AS Rao ◽  
G Brabant
Keyword(s):  
Target Genes ◽  
Thyroid Carcinomas
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