DNA IMPRINTING

Shivangi SrivastavaM.S. Pharm

(Pharmacoinformatics)PI/288

CONTENTS

• INTRODUCTION.• GENOME IMPRINTING.• MECHANISM OF IMPRITING.• PARDOR WILLI SYNDROME.• ANGELMAN SYNDROME.• CONCLUSION.

INTRODUCTION

It epigenetic mechanism that produces functional differences between the paternal and maternal genomes.

Epigenetics defined as heritable changes in gene activity and expression that occur without alteration in DNA sequence

It require for normal mammalian embryogenesis.

Any disturbance in the imprinting process result in abnormal embryonic development.

GENOME IMPRINTING

• Silencing occuring through the addition of methyl group during egg/sperm formation.

• Epigenetic modifiers of gene expression such as DNA methylation, histone modification, non-RNA and higher-order chromatin formation.

Mechanism of Epigenetics

• Histone Modification .

• DNA Methylation.

Histone Acetylation & Deacetylation Histone acetylation– Histone acetyl transferases (HATs). Add acetyl groups to histone tails. Reduces positive charge and weakens interaction of histones with DNA.Histone deacetylation– Histone deacetylases (HDACs). Removes acetyl groups from histone tails. Increases interaction of DNA and histones. Represses transcription (usually).

DNA Methylation Involves the addition of a methyl group to DNA. Usually to the number 5 carbon of the cytosine pyrimidine

ring. Effect: reducing gene expression. Catalyzed by DNA methyltransferases (DNMTs). Predominantly found in CpG sites of mammalian genome.

Silencing: Methylation of CpG sites within the promoters of genes can

lead to their . silencing, a feature found in a number of human cancers (eg.

silencing of tumor suppressor genes).

DNA METHYLATION

• Effects of DNA methylation:• embryonic development and growth• Genomic imprinting• X-chromosome inactivation

Mechanisms of Imprinting

IgF2 is an imprinted gene ,being expressed from the paternal.

PATERNAL

MATERNAL

H19 gene is an imprinted gene exprssed only from maternal.

Mechanisms of Imprinting

PARDER WILLI SYNDROME

Inherit mutated allele from the father while the allele inherited from the mother is maturally silenced.(characterised by hypotonia, obesity, and hypogonadism).

ANGELMAN SYNDROME

Inherit mutated allele from the mother while the allele inherited from the father is maturally silenced.(characterised by epilepsy, tremors, and a perpetually smiling facial expression)

CONCLUSION

• It plays an essential role in mammalian development and growth.• epigenetic mechanism, mistakes in

maintaining epigenetic mark also cause imprinting disorders.