Sandbox Reserved 1120: Difference between revisions

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The binding of SRY on DNA is specific. The DNA target site is a DNA octamer :
The binding of SRY on DNA is specific. The DNA target site is a DNA octamer :


<center><div style="width:90%; padding-top: 10px; padding-bottom: 10px;border: 1px dashed #A0A0A0; text-align: center;background: #DCFEDA;"><small>
<center><div style="width:30%; padding-top: 10px; padding-bottom: 10px;border: 1px dashed #A0A0A0; text-align: center;background: #DCFEDA;"><small>
(5'-dGCACAAAC)<br/>
(5'-dGCACAAAC)<br/>
(5'-dGTTTGTGC)
(5'-dGTTTGTGC)
</small></div></center>
</small></div></center>


This sequenece is found in the promoters of genes expressed during the testicular development
This sequence is found in the promoters of genes expressed during the testicular development.
The bend of DNA permits the recruitment of different proteins and the build of massives proteins-DNA complexes that could change the expression of different genes. It is the role of a transcription factor.<ref>PMID:11563911</ref>
The bend of DNA enables the recruitment of different proteins and the building of massive proteins-DNA complexes that could change the expression of different genes<ref>PMID:11563911</ref>.


Even if the most important function of the HMG box is its capacity of binding and bending DNA, it is also involved in DNA condensation, recombination and DNA repair.
Even if the most important function of the HMG box is binding and bending DNA, it is also involved in DNA condensation, recombination and repair.


There are 2 kinds of protein that contain a HMG box
There are two kinds of proteins that contain a HMG box:
* HMG1 : It is expressed in few cell types. It is found in transcription factors that contain a single HMG box. The bind to a DNA sequence is specific.
* '''HMG1''' : It is expressed in few cell types. It is found in transcription factors that contain a single HMG box. The binding of a DNA sequence is specific.
* HMG2 : Are found in all cell types and are abundant in chromatin. This proteins can contain two or more HMG boxes that can nonspecifically bind DNA.  
* '''HMG2''' : It is found in all cell types and is abundant in chromatin. These proteins can contain two or more HMG boxes that can non-specifically bind DNA.  


===General structure of SRY===
===General structure of SRY===
The overall structure of SRY is organized aroud the HMG-box.
 
The overall structure of SRY is organized around the HMG-box.
3 domains:
3 domains:
* N-term domain
* N-term domain
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===Sex determining===
===Sex determining===


:It acts like a sex determinator thanks to it transcriptionnal activity. It inhibits the developpement of female sex structure in th embryonnic individual.
It acts like a sex determining factor thanks to its transcriptional activity. It inhibits the development of female sex structures in the embryonic individual.


The SRY protein is a transcription factor, which contains nuclear localization domains in N terminal and C terminal. An acetylation on these domains allows to export the protein SRY in the nucleus.  <ref>Harley VR, Clarkson MJ, Argentaro A. The Molecular Action and Regulation of the Testis-Determining Factors, SRY (Sex-Determining Region on the Y Chromosome) and SOX9 [SRY-Related High-Mobility Group (HMG) Box 9]. Endocr Rev. 2003 Aug 1;24(4):466–87. [http://press.endocrine.org/doi/10.1210/er.2002-0025?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub%3Dpubmed&]</ref>
The SRY protein contains nuclear localization signals in N and C terminals. An acetylation of these domains allows the exportation of the SRY protein to the nucleus<ref>Harley VR, Clarkson MJ, Argentaro A. The Molecular Action and Regulation of the Testis-Determining Factors, SRY (Sex-Determining Region on the Y Chromosome) and SOX9 [SRY-Related High-Mobility Group (HMG) Box 9]. Endocr Rev. 2003 Aug 1;24(4):466–87. [http://press.endocrine.org/doi/10.1210/er.2002-0025?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub%3Dpubmed&]</ref>.


The SRY protein activates the SOX9 (SRY-box9) gene <ref> McElreavey K, Barbaux S, Ion A, Fellous M. The genetic basis of murine and human sex determination: a review. Heredity. 1995 Dec;75 ( Pt 6):599–611. [http://www.ncbi.nlm.nih.gov/pubmed/8575930]</ref>., this gene is found in the 17 chromosom in the long arm 24.3 <ref> NCBI [http://www.ncbi.nlm.nih.gov/gene/6662] </ref> and is implicated in the stimulation of the differentiation of pre-Sertori cells as Sertoli cells rather than granulosa cells.
The SRY protein activates the ''SOX9'' (SRY-box9) gene <ref> McElreavey K, Barbaux S, Ion A, Fellous M. The genetic basis of murine and human sex determination: a review. Heredity. 1995 Dec;75 ( Pt 6):599–611. [http://www.ncbi.nlm.nih.gov/pubmed/8575930]</ref>. This gene is found in long arm 24.3 of the chromosome 17<ref> NCBI [http://www.ncbi.nlm.nih.gov/gene/6662] </ref> and is implicated in the stimulation of the differentiation of pre-Sertori into Sertoli cells rather than granulosa cells.


The activation of sox 9 are done with protein SRY and another transcriptional factor: SF1 (steroidogenic factor 1). These transcriptional factors are bind in an enhancers called: TESCO (testis-specific enhancer of Sox9 core element). The fixation of transcriptional factor in enhancer provokes a curvature of DNA (90°C) allowing a stabilisation of the elongation complex on the SOX9 promoter. The SOX 9 protein activates the gene AMH (anti-mullerian hormone)<ref>[http://www.ebi.ac.uk/interpro/entry/IPR006799?q=AMH] </ref> allows the reduction of the channels of Müller in male. <ref>Harley VR, Clarkson MJ, Argentaro A. The Molecular Action and Regulation of the Testis-Determining Factors, SRY (Sex-Determining Region on the Y Chromosome) and SOX9 [SRY-Related High-Mobility Group (HMG) Box 9]. Endocr Rev. 2003 Aug 1;24(4):466–87. [http://press.endocrine.org/doi/10.1210/er.2002-0025?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub%3Dpubmed&]</ref>
The activation of ''SOX''9 is done by the SRY protein and another transcriptional factor: SF1 (steroidogenic factor 1). These transcriptional factors are bound on an enhancer called: TESCO (Testis-Specific Enhancer of ''SOX9'' core element). The binding of a transcriptional factor on an enhancer provokes a curvature of the DNA (≈75°), allowing a stabilization of the elongation complex on the ''SOX9'' promoter. The SOX9 protein activates the gene ''AMH'' (Anti-Mullerian Hormone)<ref>[http://www.ebi.ac.uk/interpro/entry/IPR006799?q=AMH] </ref>. Therefor, it allows the reduction of the channels of Müller in male. <ref>Harley VR, Clarkson MJ, Argentaro A. The Molecular Action and Regulation of the Testis-Determining Factors, SRY (Sex-Determining Region on the Y Chromosome) and SOX9 [SRY-Related High-Mobility Group (HMG) Box 9]. Endocr Rev. 2003 Aug 1;24(4):466–87. [http://press.endocrine.org/doi/10.1210/er.2002-0025?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub%3Dpubmed&]</ref>




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