STUDY OF HUMAN PREGNANCY SPECIFIC GLYCOPROTEIN GENE EXPRESSION DURING TROPHOBLAST DIFFERENTIATION

CAMOLOTTO S.; RACCA A.; RENA V.; PATRITO L.; GENTI-RAIMONDI S.; PANZETTA-DUTARI G.

Carlos Paz, Cordoba, Argentina

Congreso; Argentine Society for Biochemistry and Molecular Biology (SAIB); 2008

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

<!-- /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin:0cm; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman";} @page Section1 {size:595.3pt 841.9pt; margin:70.85pt 3.0cm 70.85pt 3.0cm; mso-header-margin:35.4pt; mso-footer-margin:35.4pt; mso-paper-source:0;} div.Section1 {page:Section1;} --> Human pregnancy-specific glycoproteins (PSG) gene family is composed by 11 members with above 90% sequence similarity. Their expression is an early biochemical marker of trophoblast differentiation and reduced levels of PSG proteins are associated with a poor pregnancy outcome. In this report we demonstrated a differential expression pattern for individual PSG genes by qPCR in two differentiation models, choriocarcinoma JEG3 cells and primary trophoblasts. Transient transfection assays of PSG genes constructs revealed that the promoter region governs differentiation-dependent activation in isolated primary trophoblasts. Meanwhile, the 5’ proximal regulatory region is required to mediate transcriptional activation in JEG3 cells induced to differentiate. Epigenetic regulation of PSG genes was evaluated by treating JEG3 cells with histone deacetylases inhibitors, Trichostatin A and sodium butyrate. Both reagents increased endogen PSG transcripts and protein production in a dose-dependent manner, as determined by qPCR and immunofluorescence. We conclude that PSG genes are transcriptionaly activated during trophoblasts syncytialization reaching different expression levels among them. This activation involves regulatory elements and changes in trans-acting factors levels, as well as modifications in chromatin structure. Supported by CONICET, FONCyT and SECyT-UNC.