Francis Poulat

Publications (61) View all

• Article: Isolated 'idiopathic' micropenis: hidden genetic defects?

  F Paris, K De Ferran, A Bhangoo, S Ten, N Lahlou, F Audran, N Servant, F Poulat, P Philibert, C Sultan
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  ABSTRACT: Micropenis is defined as a stretched penile length of less than 2-2.5SD for age. Aetiologies include hypogonadotropic hypogonadism, testicular dysgenesis, defects in testosterone synthesis, androgen resistance [5α-reductase (5αR) deficiency or partial androgen insensitivity] and other rare causes like growth hormone GH deficiency. Often, the cause remains unknown. The aim of this study was to determine whether isolated micropenis with normal plasma testosterone could hide a molecular defect in the androgen pathway. Twenty-six boys with isolated micropenis were included in this study. All of them had 46,XY karyotype, normal luteinizing hormone and follicle-stimulating hormone and a normal plasma testosterone response to human chorionic gonadotropin testing. Androgen receptor (AR), 5αR and steroidogenic factor 1 (SF1) genes were sequenced. A mutation in the AR gene was found in two patients, and a new mutation in the SF1 gene was found in one patient who was the only one to have a low level of inhibin B (InhB). This is the first report of isolated micropenis as a revealing symptom of AR and SF1 mutations. Anti-Mullerian hormone and InhB should thus be evaluated in patients with isolated micropenis, even when plasma testosterone is in the normal range. Detection of gene mutations is helpful for diagnosis, treatment and genetic counselling for probands.
  International Journal of Andrology 04/2011; 34(6 Pt 2):e518-25. · 3.59 Impact Factor
• Article: MiniSOX9, a dominant-negative variant in colon cancer cells.

  R Abdel-Samad, H Zalzali, C Rammah, J Giraud, C Naudin, S Dupasquier, F Poulat, B Boizet-Bonhoure, S Lumbroso, K Mouzat, C Bonnans, C Pignodel, P Raynaud, P Fort, C Quittau-Prévostel, P Blache
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  ABSTRACT: Inherited and acquired changes in pre-mRNA processing have significant roles in human diseases, especially cancer. Characterization of aberrantly spliced mRNAs may thus contribute to understand malignant transformation. We recently reported an anti-oncogenic potential for the SOX9 transcription factor in the colon. For instance, the Sox9 gene knock out in the mouse intestine results in an excess of proliferation with appearance of hyperplasia. SOX9 is expressed in colon cancer cells but its endogenous activity is weak. We looked for SOX9 variants that may impair SOX9 activity in colon cancer cells and we discovered MiniSOX9, a truncated version of SOX9 devoid of transactivation domain as a result of retention of the second intron. A significant overexpression of MiniSOX9 mRNA in human tumor samples compared with their matched normal tissues was observed by real-time reverse transcriptase-PCR. Immunohistochemistry revealed that MiniSOX9 is expressed at high levels in human colon cancer samples whereas it is undetectable in the surrounding healthy tissues. Finally, we discovered that MiniSOX9 behaves as a SOX9 inhibitor, inhibits protein kinase Cα promoter activity and stimulates the canonical Wnt pathway. This potential oncogenic activity of the SOX9 locus gives new insights on its role in colon cancer.
  Oncogene 02/2011; 30(22):2493-503. · 6.37 Impact Factor
• Article: CEACAM1, a SOX9 direct transcriptional target identified in the colon epithelium.

  H Zalzali, C Naudin, P Bastide, C Quittau-Prévostel, C Yaghi, F Poulat, P Jay, P Blache
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  ABSTRACT: A deletion of the transcription factor SOX9 gene in the mice intestine affects the morphology of the colon epithelium and leads to hyperplasia. Nevertheless, direct transcriptional targets of SOX9 in this tissue are still unknown. A microarray analysis identified the tumor suppressor carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) as a possible SOX9 target gene and we demonstrate here that SOX9 upregulates CEACAM1 in human colonic cells. Moreover, CEACAM1 expression is reduced in colon of SOX9-deficient mouse, suggesting an important function for SOX9 in the transcriptional activation of the CEACAM1 gene. We further identified SOX9-binding sequences in the human and rat CEACAM1 promoters, and an electrophoretic mobility shift together with a chromatin immunoprecipitation provided an additional evidence of the SOX9 binding to the human promoter. In addition, we established that histone acyl-transferase p300 behaves as an SOX9 co-activator of the rat and human CEACAM1promoters. These results highlight CEACAM1 as the first direct target of SOX9 identified in the colon epithelium.
  Oncogene 10/2008; 27(56):7131-8. · 6.37 Impact Factor
• Article: Male specific expression of lipocalin-type prostaglandin D synthase (cPTGDS) during chicken gonadal differentiation: relationship with cSOX9.

  B Moniot, B Boizet-Bonhoure, F Poulat
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  ABSTRACT: As in mammals, the SOX9 gene (cSOX9) is specifically expressed in male differentiating Sertoli cells during chicken gonadal development. Recent studies in mouse have shown that the prostaglandin D(2) (PGD(2))/lipocalin-type prostaglandin D synthase (PTGDS) pathway is functionally associated with the regulation of SOX9 and is specifically expressed in male developing gonads. In this study, we have shown that, as in mammals, cPTGDS is a male specific gene during chicken testicular development and is temporally expressed in the same window as cSOX9 in Sertoli cells. Using a culture of gonadal explants, we have shown that exogenous PGD(2) enhances cSOX9 expression in male, and activates its ectopic expression in female gonads without up-regulating cAMH. These data indicate a conserved PGD(2) modulation of SOX9 expression during testicular differentiation between birds and mammals.
  Sexual Development 02/2008; 2(2):96-103. · 2.27 Impact Factor
• Article: SOX7 transcription factor: sequence, chromosomal localisation, expression, transactivation and interference with Wnt signalling.

  W Takash, J Cañizares, N Bonneaud, F Poulat, M G Mattéi, P Jay, P Berta
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  ABSTRACT: The Sox gene family consists of several genes related by encoding a 79 amino acid DNA-binding domain known as the HMG box. This box shares strong sequence similarity to that of the testis determining protein SRY. SOX proteins are transcription factors having critical roles in the regulation of diverse developmental processes in the animal kingdom. We have characterised the human SOX7 gene and compared it to its mouse orthologue. Chromosomal mapping analyses localised mouse Sox7 on band D of mouse chromosome 14, and assigned human SOX7 in a region of shared synteny on human chromosome 8 (8p22). A detailed expression analysis was performed in both species. Sox7 mRNA was detected during embryonic development in many tissues, most abundantly in brain, heart, lung, kidney, prostate, colon and spleen, suggesting a role in their respective differentiation and development. In addition, mouse Sox7 expression was shown to parallel mouse Sox18 mRNA localisation in diverse situations. Our studies also demonstrate the presence of a functional transactivation domain in SOX7 protein C-terminus, as well as the ability of SOX7 protein to significantly reduce Wnt/beta-catenin-stimulated transcription. In view of these and other findings, we suggest different modes of action for SOX7 inside the cell including repression of Wnt signalling.
  Nucleic Acids Research 12/2001; 29(21):4274-83. · 8.03 Impact Factor