Biology Reference
In-Depth Information
CHAPTER TWO
Functions of DNA Methylation
and Hydroxymethylation in
Mammalian Development
Sylvain Guibert, Michael Weber
1
Biotechnology and Cell Signaling, University of Strasbourg, CNRS/UMR7242, Illkirch, Strasbourg, France
1
Corresponding author: e-mail address: michael.weber@unistra.fr
Contents
1.
Introduction
48
2. Enzymatic Players
49
2.1 DNA methyltransferases
49
2.2 Proteins of the TET family
52
3. Patterns of DNA Methylation and Hydroxymethylation During Development
54
3.1 Distribution of 5mC in mammalian genomes
54
3.2 Distribution of 5hmC in mammalian genomes
58
3.3 Reprogramming of DNA methylation during preimplantation development
59
3.4 Reprogramming of DNA methylation in gametes
61
3.5 Global demethylation in erythropoiesis
62
4. Role of Cytosine Methylation in Genome Regulation
62
4.1 Genomic imprinting and X inactivation
62
4.2 Regulation of lineage-specific gene expression
64
4.3 Does DNA methylation influence RNA processing?
66
4.4 Maintenance of genome integrity
67
5. Emerging Functions of Cytosine Hydroxymethylation
68
5.1 Role in DNA methylation erasure
68
5.2 Putative roles in gene regulation
70
6. Conclusions
71
Acknowledgments
72
References
72
Abstract
DNA methylation occurs at cytosines, predominantly in the CpG dinucleotide context
and is a key epigenetic regulator of embryogenesis and stem-cell differentiation in
mammals. The genomic patterns of 5-methylcytosine are extensively reprogrammed
during early embryonic development as well as in the germ-cell lineage. Thanks to
improvements in high-throughput mapping technologies, it is now possible to charac-
terize the dynamics of this epigenetic mark at the genome scale. DNA methylation plays
