Expression and Imprinting Status of Human PEG8/IGF2AS, a Paternally Expressed Antisense Transcript from the IGF2 Locus, in Wilms' Tumors

Okutsu, Tomohisa; Kuroiwa, Yoshimi; Kagitani, Fusako; Kai, Masayuki; Aisaka, Kohzo; Tsutsumi, Osamu; Kaneko, Yasuhiko; Yokomori, Kinji; Surani, M. Azim; Kohda, Takashi; Kaneko-Ishino, Tomoko; Ishino, Fumitoshi

doi:10.1093/oxfordjournals.jbchem.a022630

Cited by 69 publications

(43 citation statements)

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“…Promoter-specific imprinting has previously been demonstrated in the human IGF2 gene (13,14) and in the human (and murine) GNAS gene (15,16). Paternally expressed antisense transcripts, IGF2-AS and GNAS-AS, were found in both imprinted regions (15)(16)(17)(18).…”

Section: Resultsmentioning

confidence: 90%

An Imprinted PEG1/MEST Antisense Expressed Predominantly in Human Testis and in Mature Spermatozoa

Li¹,

Vu²,

Lee³

et al. 2002

Journal of Biological Chemistry

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PEG1 (or MEST)is an imprinted gene located on human chromosome 7q32 that is expressed predominantly from the paternal allele. In the mouse, Peg1/Mest is associated with embryonic growth and maternal behavior. Human PEG1 is transcribed from two promoters; the transcript from promoter P1 is derived from both parental alleles, and the transcript from P2 is exclusively from the paternal allele. We characterized the P1 and P2 transcripts in various normal and neoplastic tissues. In the normal tissues, PEG1 was transcribed from both promoters P1 and P2, whereas in six of eight neoplastic tissues, PEG1 was transcribed exclusively from promoter P1. Bisulfite sequencing demonstrated high levels of CpG methylation in the P2 region of DNA from a lung tumor. In the region between P1 and P2, we identified a novel transcript, PEG1-AS, in an antisense orientation to PEG1. PEG1-AS is a spliced transcript and was detected as a strong 2.4-kilobase band on a Northern blot. PEG1-AS and PEG1 P2-sense transcript were expressed exclusively from the paternal allele. Fragments of DNA from within the 1.5-kilobase region between PEG1-AS and the P2 exon were ligated to a pGL3 luciferase reporter vector and transfected into NCI H23 cells. This DNA exhibited strong promoter activity in both the sense and antisense directions, indicating that PEG1-AS and P2 exon share a common promoter region. Treatment of the transfected DNA fragments with CpG methylase abolished the promoter activity. Of interest, PEG1-AS was expressed predominantly in testis and in mature motile spermatozoa, indicating a possible role for this transcript in human sperm physiology and fertilization.

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Section: Resultsmentioning

confidence: 90%

An Imprinted PEG1/MEST Antisense Expressed Predominantly in Human Testis and in Mature Spermatozoa

Li¹,

Vu²,

Lee³

et al. 2002

Journal of Biological Chemistry

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“…It remains unclear whether IGFAS regulates IGF2 or H19 imprinting; nonetheless, it may have biological importance. In Wilms' tumor, IGF2AS is highly expressed and demonstrates sporadic loss of imprinting [42,43]. As stated before, disrupted IGF2 imprinting is implicated in a number of diseases, and can be attributed to increased gene dosage and subsequent increases in IGF2 signaling, which will be discussed in the following section.…”

Section: Igf2 Imprinting As a Model Of Allele-specific Repressionmentioning

confidence: 94%

“…Multiple sense and antisense transcripts have been detected in the mouse Igf2 5' region, and the major antisense transcript, Igf2AS, is paternally expressed and noncoding [41]. An antisense message transcribed from a homologous region near human IGF2 encodes a putative 273-amino acid protein of unknown function [42]. It remains unclear whether IGFAS regulates IGF2 or H19 imprinting; nonetheless, it may have biological importance.…”

Section: Igf2 Imprinting As a Model Of Allele-specific Repressionmentioning

confidence: 99%

IGF2: Epigenetic regulation and role in development and disease

Chao

D'Amore

2008

Cytokine & Growth Factor Reviews

265

211

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Insulin-like growth factor II (IGF2) is perhaps the most intricately regulated of all growth factors characterized to date. Its gene is imprinted-only one allele is active, depending on parental origin -and this pattern of expression is maintained epigenetically in almost all tissues. IGF2 activity is further controlled through differential expression of receptors and IGF-binding proteins (IGFBPs) that determine protein availability. This complex and multifaceted regulation emphasizes the importance of accurate IGF2 expression and activity. This review will examine the regulation of the IGF2 gene and what it has revealed about the phenomenon of imprinting, which is frequently disrupted in cancer. IGF2 protein function will be discussed, along with diseases that involve IGF2 overexpression. Roles for IGF2 in sonic hedgehog (Shh) signaling and angiogenesis will also be explored.

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“…Another imprinted gene implicated in cancer is a paternally expressed antisense RNA, PEG8/IGF2AS, that is transcribed from the IGF2 locus (Szymanski et al 2005). IGF2AS shows significantly elevated expression levels in Wilms' tumors and several fetal tumors but not in normal kidney tissue (Okutsu et al 2000).…”

Section: Linking Ncrna and Cancermentioning

confidence: 99%

Eukaryotic regulatory RNAs: an answer to the ‘genome complexity’ conundrum

Prasanth¹,

Spector²

2007

Genes Dev.

363

303

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A large portion of the eukaryotic genome is transcribed as noncoding RNAs (ncRNAs). While once thought of primarily as "junk," recent studies indicate that a large number of these RNAs play central roles in regulating gene expression at multiple levels. The increasing diversity of ncRNAs identified in the eukaryotic genome suggests a critical nexus between the regulatory potential of ncRNAs and the complexity of genome organization. We provide an overview of recent advances in the identification and function of eukaryotic ncRNAs and the roles played by these RNAs in chromatin organization, gene expression, and disease etiology.

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Expression and Imprinting Status of Human PEG8/IGF2AS, a Paternally Expressed Antisense Transcript from the IGF2 Locus, in Wilms' Tumors

Cited by 69 publications

References 0 publications

An Imprinted PEG1/MEST Antisense Expressed Predominantly in Human Testis and in Mature Spermatozoa

An Imprinted PEG1/MEST Antisense Expressed Predominantly in Human Testis and in Mature Spermatozoa

IGF2: Epigenetic regulation and role in development and disease

Eukaryotic regulatory RNAs: an answer to the ‘genome complexity’ conundrum

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