DNA Methylation Regulates Placental Lactogen I Gene Expression

Abstract

Expression of rat placental lactogen I is specific to the placenta and never expressed in other tissues. To obtain insight into the mechanism of tissue-specific gene expression, we investigated the methylation status in 3.4 kb of the 5'-flanking region of the rat placental lactogen I gene. We found that the distal promoter region of the rat placental lactogen I gene had more potent promoter activity than that of the proximal area alone, which contains several possible cis-elements. Although there are only 17 CpGs in the promoter region, in vitro methylation of the reporter constructs caused severe suppression of reporter activity, and CpG sites in the placenta were more hypomethylated than other tissues. Coexpression of methyl-CpG-binding protein with reporter constructs elicited further suppression of the reporter activity, whereas treatment with trichostatin A, an inhibitor of histone deacetylase, reversed the suppression caused by methylation. Furthermore, treatment of rat placental lactogen I nonexpressing BRL cells with 5-aza-2'-deoxycytidine, an inhibitor of DNA methylation, or trichostatin A resulted in the de novo expression of rat placental lactogen I. These results provide evidence that change in DNA methylation is the fundamental mechanism regulating the tissue-specific expression of the rat placental lactogen I gene.

The Human Placental Methylome

“…However, this is very much gene specific. Some examples of genes with placental-specific expression that are also specifically unmethylated at their gene promoters include chorionic gonadotropin-beta subunit (CGB) (Campain et al 1993) and placental lactogen (CSH1) (Cho et al 2001). Likewise, many genes are methylated at their promoter and down-regulated specifically in the placenta.…”

DNA methylation profile of tissue-dependent and differentially methylated regions (T-DMRs) in mouse promoter regions demonstrating tissue-specific gene expression

“…Epigenetic systems are recognized as memory systems for these inheritable gene functions and, in mammals, they comprise DNA methylation and histone modifications of chromatin. DNA methylation in tissue-dependent and differentially methylated regions (T-DMRs) is involved in expression of tissue-specific genes as well as expression of key transcription factors that constitute transcription networks governing tissue or cell specificity (Shen and Maniatis 1980;Cho et al 2001;Imamura et al 2001;Hattori et al 2004bHattori et al , 2007Nishino et al 2004). Abnormal methylation of T-DMRs has been implicated in the pathogenesis of certain diseases (Jones 2002;Ushijima 2005).…”

Identification of Genetic and Epigenetic Similarities of SPHK1/Sphk1 in Mammals

“…DNA methylation analysis: In order to determine the DNA methylation status of individual CpG sites, genomic DNA was sequenced following bisulfite modification, as described previously [5,8]. Briefly, 10 µg of Pvu II (TaKaRa; Kyoto, Japan) -digested genomic DNA was initially denatured with 330 mM NaOH.…”