Biology Reference
In-Depth Information
CHAPTER ONE
Cell and Molecular Biology
of DNA Methyltransferase 1
K. Naga Mohan
*
, J. Richard Chaillet
†,1
*
Department of Biological Sciences, Birla Institute of Technology and Science Pilani, Hyderabad Campus,
Hyderabad, Andhra Pradesh, India
†
Department of Microbiology and Molecular Genetics, Magee-Womens Research Institute, University
of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
1
Corresponding author: e-mail address: chaillet@pitt.edu
Contents
1.
Introduction
2
2. Positions of Genomic 5-Methyl-Cytosines and Their Significance
3
2.1 Symmetric and asymmetric cytosine methylation in plants and animals
3
2.2 Significance of symmetric methylation
5
2.3 Holliday/Pugh and Riggs postulates for inheritance of symmetric cytosine
methylation
6
2.4 Experimental support for maintenance methyltransferase activity
7
3. Basic Molecular Mechanisms of Maintenance Methylation
9
3.1 Basic chemistry of enzymatic reaction
9
3.2 Similarities and differences in plant and animal maintenance
methyltransferases
10
3.3 Structured, highly conserved regions of DNMT1 and possible functions
13
3.4 Role of accessory and interacting proteins in DNMT1 methyltransferase
function
16
3.5 Intrinsically disordered region of DNMT1 and possible functions
18
3.6 Roles of posttranslational modifications to DNMT1
18
4. Genomic Methylation During Plant and Animal Life Cycles
19
4.1 Patterns of symmetric methylation during mouse development
19
4.2 Developmental patterns require de novo methylation, maintenance
methylation, and demethylation
21
4.3 Regulation of Dnmt1 expression
21
4.4 DNMT1's role in imprinting
23
4.5 DNMT1 and development
25
4.6 Roles for Dnmt1 in DNA repair and radiation-induced DNA damage
26
5. Demethylation
27
5.1 Lessons from plants—Developmental, biochemical, and genetic studies
27
5.2 Evidence for active demethylation in animals
29
5.3 Active versus passive demethylation
32
5.4 Regulating DNMT1 and demethylation
32
