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

• Published in: PloS one 2016-04, Vol.11 (4), p.e0154216-e0154216
• Main Authors: Kim, Joomyeong, Ye, An
• Format: Article
• Language: English
• Subjects: Analysis; Animals; Base Sequence; Binding Sites - genetics; Biology and life sciences; Cell division; Chromatin Immunoprecipitation; Deoxyribonucleic acid; DNA; DNA binding; DNA Methylation; E-Box Elements - genetics; Enhancer Elements, Genetic - genetics; Enhancers; Epigenetic inheritance; Epigenetics; Epigenomics - methods; Female; Footprinting; Gene Expression Regulation; Gene regulation; Genes; Genomes; Humans; Kruppel-Like Transcription Factors - classification; Kruppel-Like Transcription Factors - genetics; Mammals; Marsupials; Medicine and Health Sciences; Mice, Inbred C57BL; Musculoskeletal system; MyoD protein; MyoD Protein - metabolism; Myogenesis; NF-κB protein; Nucleotide Motifs - genetics; Ovarian cancer; Peg3 protein; Phylogenetics; Phylogeny; Protein Binding; Proteins; Regulatory sequences; Regulatory Sequences, Nucleic Acid - genetics; Research and Analysis Methods; Sequence Homology, Amino Acid; Transcription; Transcription, Genetic; Tumorigenesis
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0154216

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.