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PMID: 9887097 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Cytosine methylation and mammalian development.

Genes & development ·Vol. 13 ·No. 1 ·1999-01-01 ·Pages 26-34

Walsh CP, Bestor TH

Abstract

Programmed methylation and demethylation of regulatory sequences has been proposed to play a central role in vertebrate development. We report here that the methylation status of the 5' regions of a panel of tissue-specific genes could not be correlated with expression in tissues of fetal and newborn mice. Genes reported to be regulated by reversible methylation were not expressed ectopically or precociously in Dnmt1-deficient mouse embryos under conditions where demethylation caused biallelic expression of imprinted genes and activated transcription of endogenous retroviruses of the IAP class. These and other data suggest that the numerous published expression-methylation correlations may have described not a cause but a consequence of transcriptional activation. A model is proposed under which cytosine methylation represents a biochemical specialization of large genomes that participates in specialized biological functions such as allele-specific gene expression and the heritable transcriptional silencing of parasitic sequence elements, whereas cellular differentiation is controlled by conserved regulatory networks that do not depend on covalent modification of the genome.

MeSH Terms
Alleles Animals CpG Islands/genetics Cytosine/metabolism DNA (Cytosine-5-)-Methyltransferases/deficiency,genetics DNA Methylation Embryo, Mammalian/metabolism Gene Expression Regulation, Developmental/genetics Mammals Mice Promoter Regions, Genetic/genetics RNA, Messenger/analysis Regulatory Sequences, Nucleic Acid/genetics Transcriptional Activation/genetics
Chemicals
RNA, Messenger Cytosine DNA (Cytosine-5-)-Methyltransferases
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Walsh C P
Department of Genetics and Development, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA.
Bestor T H
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.13.1.26
Published
1999-01-01
Pages
26-34
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC316374
Subset
IM
External Links
PubMed source DOI: 10.1101/gad.13.1.26 PMC Full Text View journal details
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