HUMAN PREGNANCY SPECIFIC GLYCOPROTEIN (PSG) GENE EXPRESSION IS UP-REGULATED BY LYSINE ACETYLATION INVOLVING HISTONE AND NONHISTONE PROTEIN

SOLEDAD A. CAMOLOTTO; ANA C. RACCA; MAGALÍ E. RIDANO; SUSANA GENTI-RAIMONDI; GRACIELA M. PANZETTA-DUTARI

Foz de Iguazú

Congreso; V SLIMP - IV LASRI Meeting 2013; 2013

Latin American Society for Maternal Fetal Interaction and Placenta

PSGs, the major secreted syncytiotrophoblastic proteins, are early markers of cytotrophoblast differentiation and low levels are associated with complicated pregnancies. However, mechanisms controlling their expression are far from been fully understood. Pharmacological inhibition of histone deacetylases, in JEG-3cells, up-regulated PSGs expression, and augmented the amount of acetylated histone H3 associated with their 5´regulatory regions. Sp1- and KLF6- PSG5 promoter activation was markedly enhanced in the presence of trichostatin A, correlating with an increase in Sp1 acetylation and KLF6 nuclear localization. The co-activators PCAF, p300, and CBP enhanced Sp1-dependent PSG5 promoter activation through their histone acetyltransferase function. Instead, p300 and CBP acetyltransferase domain was dispensable for sustaining co-activation of PSG5 promoter by KLF6. Results are consistent with a regulatory role of lysine acetylation on PSGs expression through a relaxed chromatin state and an increase in the transcriptional activity of Sp1 and KLF6. These mechanisms might contribute with PSGs up-regulation in a successful pregnancy .