Phylogenetic and Epigenetic Footprinting of the Putative Enhancers of the Peg3 Domain.

Joomyeong Kim,An Ye,Martina Stromvik

doi:10.1371/journal.pone.0154216

Abstract

The Peg3 (Paternally Expressed Gene 3) imprinted domain is predicted to be regulated through a large number of evolutionarily conserved regions (ECRs) that are localized within its middle 200-kb region. In the current study, we characterized these potential cis-regulatory regions using phylogenetic and epigenetic approaches. According to the results, the majority of these ECRs are potential enhancers for the transcription of the Peg3 domain. Also, these potential enhancers can be divided into two groups based on their histone modification and DNA methylation patterns: ubiquitous and tissue-specific enhancers. Phylogenetic and bioinformatic analyses further revealed that several cis-regulatory motifs are frequently associated with the ECRs, such as the E box, PITX2, NF-κB and RFX1 motifs. A series of subsequent ChIP experiments demonstrated that the trans factor MYOD indeed binds to the E box of several ECRs, further suggesting that MYOD may play significant roles in the transcriptional control of the Peg3 domain. Overall, the current study identifies, for the first time, a set of cis-regulatory motifs and corresponding trans factors that may be critical for the transcriptional regulation of the Peg3 domain.

Highlights

Peg3 (Paternally expressed gene 3) is an imprinted gene identified from human chromosome 19q13.4/mouse proximal chromosome 7 [1]
Phylogenetic and bioinformatic analyses further revealed that several cis-regulatory motifs are frequently associated with the evolutionarily conserved regions (ECRs), such as the E box, PITX2, NF-κB and RFX1 motifs
A series of subsequent Chromatin ImmunoPrecipitation (ChIP) experiments demonstrated that the trans factor MYOD binds to the E box of several ECRs, further suggesting that MYOD may play significant roles in the transcriptional control of the Peg3 domain

Summary

Introduction

Peg (Paternally expressed gene 3) is an imprinted gene identified from human chromosome 19q13.4/mouse proximal chromosome 7 [1]. Recent studies further characterized Peg as a transcriptional repressor controlling various downstream genes [7,8]. PEG3 has been often identified as a potential tumor suppressor based on the observation that its promoter is usually methylated in ovarian and breast cancers [9,10,11]. According to recent surveys in humans and mice, PEG3 appears to be one of the most epigenetically unstable imprinted genes during tumorigenesis [12,13]. In vitro experiments demonstrated that the PEG3 protein has the potential to stop cell division in ovarian cancer cell lines [14]. The expression levels of Peg are dynamically fluctuated in response to various intrinsic and environmental cues, including nutritional starvation and hypoxic conditions

Methods

Results

Conclusion