Parental imprinting regulates insulin-like growth factor signaling: a Rosetta Stone for understanding the biology of pluripotent stem cells, aging and cancerogenesis
In recent years, solid evidence has accumulated that insulin-like growth factor-1 (IGF-1) and 2 (IGF-2) regulate many biological processes in normal and malignant cells. Recently, more light has been shed on the epigenetic mechanisms regulating expression of genes involved in IGF signaling (IFS) and...
Gespeichert in:
Veröffentlicht in: | Leukemia 2013-04, Vol.27 (4), p.773-779 |
---|---|
Hauptverfasser: | , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
Zusammenfassung: | In recent years, solid evidence has accumulated that insulin-like growth factor-1 (IGF-1) and 2 (IGF-2) regulate many biological processes in normal and malignant cells. Recently, more light has been shed on the epigenetic mechanisms regulating expression of genes involved in IGF signaling (IFS) and it has become evident that these mechanisms are crucial for initiation of embryogenesis, maintaining the quiescence of pluripotent stem cells deposited in adult tissues (for example, very-small embryonic-like stem cells), the aging process, and the malignant transformation of cells. The expression of several genes involved in IFS is regulated at the epigenetic level by imprinting/methylation within differentially methylated regions (DMRs), which regulate their expression from paternal or maternal chromosomes. The most important role in the regulation of IFS gene expression is played by the
Igf-2
-
H19
locus, which encodes the autocrine/paracrine mitogen IGF-2 and the
H19
gene, which gives rise to a non-coding RNA precursor of several microRNAs that negatively affect cell proliferation. Among these, miR-675 has recently been demonstrated to downregulate expression of the IGF-1 receptor. The proper imprinting of DMRs at the
Igf-2-H19
locus, with methylation of the paternal chromosome and a lack of methylation on the maternal chromosome, regulates expression of these genes so that
Igf-2
is transcribed only from the paternal chromosome and
H19
(including miR-675) only from the maternal chromosome. In this review, we will discuss the relevance of (i) proper somatic imprinting, (ii) erasure of imprinting and (iii) loss of imprinting within the DMRs at the
Igf-2-H19
locus to the expression of genes involved in IFS, and the consequences of these alternative patterns of imprinting for stem cell biology. |
---|---|
ISSN: | 0887-6924 1476-5551 |
DOI: | 10.1038/leu.2012.322 |