DNA methylation: Functional complexity in prokaryotic and eukaryotic genome regulation.

UNIVERSITY OF AGRICULTURAL SCIENCES BANGALORE

DEPARTMENT OF PLANT BIOTECHNOLOGY

GKVK, BANGALORE-65

II SEMINAR: BT 751(0+1)

Name: Mahantesha Naika B.N. Date: 12/03/2011

ID No: PAK 9058 Time: 9:30 AM

CLASS: II Ph.D, Plant Biotechnology Venue: Seminar hall

SYNOPSIS

DNA methylation: Functional complexity in prokaryotic and eukaryotic genome regulation.

The intricate and precise regulation of gene expression in space and time is fundamental for normal development in all organisms. The spatial and temporal orchestration of gene expression trajectories is primarily controlled genetically by specific DNA sequences including cis- and trans-acting elements. However, increasing evidence suggests that many aspects of development also involve epigenetic regulations. That is, the mitotically and/or meiotically inheritable yet reversible changes in gene expression without a change in DNA sequence are intimately associated with plant development. Cytosine-5 methylation is a prominent epigenetic modification, which is established and maintained by multiple, interacting cellular machineries (Meishan et al.,2010).

The phenotype of a cell is primarily determined by its expression profile and its response to environmental cues. Epigenetics provides stability and diversity to the cellular phenotype through chromatin marks that affect local transcriptional potential and that are preserved or regenerated during cell division. Methylation of DNA cytosine residues at the carbon 5 position (5meC) is a common epigenetic mark in many eukaryotes and is often found in the sequence context CpG or CpHpG (H = A, T, C). When located at gene promoters, DNA methylation is usually a repressive mark. However, CpG DNA methylation is increased in the gene bodies of actively transcribed genes in plants and mammals. Plant CpHpG methylation is found in non-expressed transposons. Bacteria and Archaea also have 5meC, along with N-4-methylcytosine and N-6-methyladenine, and these modified bases participate in restriction–modification systems and mismatch repair strand discrimination, among other roles. DNA methylation is laid down by dedicated DNA methyltransferases with highly conserved catalytic motifs. In eukaryotes, usually only a subset of potential target sequences in the genome are methylated, therefore the distribution of methyl marks can convey epigenetic information by demarcating regions of transcriptional silence or transcriptional potential. The delineation of regional DNA methylation patterns, and broader DNA methylation profiles, has important implications for understanding why certain regions of the genome can be expressed in specific developmental contexts and how epigenetic changes might enable aberrant expression patterns and disease (Peter, 2010).

Cytosine methylation is important for transposon silencing and epigenetic regulation of endogenous genes, although the extent to which this DNA modification functions to regulate the genome is still unknown. Here they reported the first comprehensive DNA methylation map of an entire genome, at 35 base pair resolution, using the flowering plant Arabidopsis thaliana as a model. They find that pericentromeric heterochromatin, repetitive sequences, and regions producing small interfering RNAs are heavily methylated. Unexpectedly, over one-third of expressed genes contain methylation within transcribed regions, whereas only 5% of genes show methylation within promoter regions. Interestingly, genes methylated in transcribed regions are highly expressed and constitutively active, whereas promoter-methylated genes show a greater degree of tissue specific expression. Whole-genome tiling-array transcriptional profiling of DNA methyltransferase null mutants identified hundreds of genes and intergenic noncoding RNAs with altered expression levels, many of which may be epigenetically controlled by DNA methylation ( Zhang et al.,2006).

Plants and animals use similar mechanistic strategies for controlling DNA methylation.Both use small-RNA based pathways to target DNA methylation to transposons,both require methyl-DNA-binding proteins to maintain DNA methylation patterns,and both show intimate connections between histones and DNA methylation marks.

MEISHAN ZHANG., JOSPHERT N., KIMATU KEZHANG XU., BAO LIU (2010), DNA cytosine methylation in plant development. J. of Genetics and Genomic. 37:1-12.

PETER W. LAIRD., 2010, Principles and challenges of genome wide DNA methylation analysis. Nature Rev. Genet. , 11: 191-203.

XIAOYU ZHANG., JUNSHI YAZAKI., AMBIKA SUNDARESAN., SHAWN COKUS., SIMON W.L., CHAN., HUAMING CHEN.,IAN R. HENDERSON., PAUL SHINN.,MATTEO PELLEGRINI.,STEVE E., JACOBSEN.,AND JOSEPH R. ECKER., 2006,Genome-wide High-Resolution Mapping and Functional Analysis of DNA Methylation in Arabidopsis. Cell., 126:1189–1201.