Domain-specific response of imprinted genes to reduced DNMT1.

Abstract:

:Imprinted genes are expressed in a monoallelic, parent-of-origin-specific manner. Clusters of imprinted genes are regulated by imprinting control regions (ICRs) characterized by DNA methylation of one allele. This methylation is critical for imprinting; a reduction in the DNA methyltransferase DNMT1 causes a widespread loss of imprinting. To better understand the role of DNA methylation in the regulation of imprinting, we characterized the effects of Dnmt1 mutations on the expression of a panel of imprinted genes in the embryo and placenta. We found striking differences among imprinted domains. The Igf2 and Peg3 domains showed imprinting perturbations with both null and partial loss-of-function mutations, and both domains had pairs of coordinately regulated genes with opposite responses to loss of DNMT1 function, suggesting these domains employ similar regulatory mechanisms. Genes in the Kcnq1 domain were less sensitive to the absence of DNMT1. Cdkn1c exhibited imprinting perturbations only in null mutants, while Kcnq1 and Ascl2 were largely unaffected by a loss of DNMT1 function. These results emphasize the critical role for DNA methylation in imprinting and reveal the different ways it controls gene expression.

journal_name

Mol Cell Biol

authors

Weaver JR,Sarkisian G,Krapp C,Mager J,Mann MR,Bartolomei MS

doi

10.1128/MCB.01278-09

subject

Has Abstract

pub_date

2010-08-01 00:00:00

pages

3916-28

issue

16

eissn

0270-7306

issn

1098-5549

pii

MCB.01278-09

journal_volume

30

pub_type

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