Human pregnancy specific glycoprotein (PSG) gene expression is up-regulated by lysine acetylation involving histone and nonhistone proteins

CAMOLOTTO, SOLEDAD; RACCA, ANA C.; RIDANO, MAGALÍ EVELIN; GENTI-RAIMONDI, SUSANA; PANZETTA-DUTARI, GRACIELA

Foz de Iguazú

Congreso; SLIMP-LASRI 2013; 2013

PSGs, the major secreted syncytiotrophoblast proteins, are early cytotrophoblast differentiation markers and low levels are associated with complicated pregnancies. However, mechanisms controlling their expression are far from being fully understood. Pharmacological inhibition of histone deacetylases in JEG-3 cells up-regulated PSG expression and augmented the acetylation of histone H3 associated with PSG 5ŕegulatory regions. Sp1- and KLF6-medited 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 PSG5 promoter co-activation by KLF6. Results are consistent with a regulatory role of lysine acetylation on PSG expression through a relaxed chromatin state and an increased transcriptional activity of Sp1 and KLF6. These mechanisms might contribute with PSG up-regulation during differentiation, necessary for a successful pregnancy.