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Vol 50, No 2 (2012)
Review paper
Submitted: 2012-07-04
Accepted: 2012-07-04
Published online: 2012-07-05
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Igf2-H19, an imprinted tandem gene, is an important regulator of embryonic development, a guardian of proliferation of adult pluripotent stem cells, a regulator of longevity, and a ‘passkey’ to cancerogenesis

Mariusz Z. Ratajczak
DOI: 10.5603/FHC.2012.0026
·
Folia Histochem Cytobiol 2012;50(2):171-179.

open access

Vol 50, No 2 (2012)
REVIEW
Submitted: 2012-07-04
Accepted: 2012-07-04
Published online: 2012-07-05

Abstract

The insulin-like growth factor-2 (Igf2)-H19 locus encodes important paternally imprinted genes that govern normal embryonic development. While Igf-2 encodes IGF2, which is an autocrine/paracrine mitogen,  transcription of H19 gives rise to non-coding mRNA that is a precursor of several microRNAs (miRNAs) that negatively affect cell proliferation. The proper imprinting of a differentially methylated region (DMR) within this locus, with methylation of the paternal chromosome and a lack of methylation on the maternal chromosome, regulates expression of both of these genes so that Igf2 is transcribed only from the paternal chromosome and H19 only from the maternal chromosome. There is growing evidence that this ‘Yin-Yang’ locus regulates embryonic development. Furthermore, recent evidence indicates that erasure of imprinting (hypomethylation) of the Igf2-H19 locus on both chromosomes, which leads to downregulation of Igf2 and upregulation of H19 expression, plays an important role in regulating quiescence of pluripotent stem cells in adult organisms, and may be involved in the regulation of lifespan. In contrast, hypermethylation of this locus on both chromosomes (loss of imprinting) results in Igf2 overexpression and is observed in several malignancies. In this review, we will discuss the biological consequences of changes in Igf2-H19 expression.

Abstract

The insulin-like growth factor-2 (Igf2)-H19 locus encodes important paternally imprinted genes that govern normal embryonic development. While Igf-2 encodes IGF2, which is an autocrine/paracrine mitogen,  transcription of H19 gives rise to non-coding mRNA that is a precursor of several microRNAs (miRNAs) that negatively affect cell proliferation. The proper imprinting of a differentially methylated region (DMR) within this locus, with methylation of the paternal chromosome and a lack of methylation on the maternal chromosome, regulates expression of both of these genes so that Igf2 is transcribed only from the paternal chromosome and H19 only from the maternal chromosome. There is growing evidence that this ‘Yin-Yang’ locus regulates embryonic development. Furthermore, recent evidence indicates that erasure of imprinting (hypomethylation) of the Igf2-H19 locus on both chromosomes, which leads to downregulation of Igf2 and upregulation of H19 expression, plays an important role in regulating quiescence of pluripotent stem cells in adult organisms, and may be involved in the regulation of lifespan. In contrast, hypermethylation of this locus on both chromosomes (loss of imprinting) results in Igf2 overexpression and is observed in several malignancies. In this review, we will discuss the biological consequences of changes in Igf2-H19 expression.

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Keywords

imprinting; Igf2; VSELs; H19; longevity; cancerogenesis

About this article
Title

Igf2-H19, an imprinted tandem gene, is an important regulator of embryonic development, a guardian of proliferation of adult pluripotent stem cells, a regulator of longevity, and a ‘passkey’ to cancerogenesis

Journal

Folia Histochemica et Cytobiologica

Issue

Vol 50, No 2 (2012)

Article type

Review paper

Pages

171-179

Published online

2012-07-05

Page views

5846

Article views/downloads

5401

DOI

10.5603/FHC.2012.0026

Bibliographic record

Folia Histochem Cytobiol 2012;50(2):171-179.

Keywords

imprinting
Igf2
VSELs
H19
longevity
cancerogenesis

Authors

Mariusz Z. Ratajczak

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