HEALTH PRESENTATION

EPIGENETIC Histone Methylation

Benhariga Ichrak, Brahimi Rawdha, Benattia Hasnia

INTRODUCTION

• Epigenetics refers to the chemical and structural modifications of chromatin, the assembly formed by DNA and the histones around which it is wrapped. These epigenetic changes do not alter the underlying DNA sequence but influence its accessibility and expression.

• Plays a key role in many biological processes:

-Embryonic development and cell differentiation-X chromosome inactivation-The parental imprint-Aging-The response to environmental factors

INTRODUCTION

• The genetic material contained in eukaryotic cells is compacted into a nucleoprotein structure called chromatin

• The fundamental unit of chromatin is the nucleosome, which consists of a histone octamer containing two copies of the four histones H2A, H2B, H3 and H4 around which 146 base pairs (bp) of DNA are wrapped.

INTRODUCTION

Chromatin is organized into domains such as euchromatin and heterochromatin which will in some cases be an obstacle to cellular processes linked to DNA (for example DNA replication, transcription, recombination and repair)

The cell has several processes for modifying the nucleosome. Among these modifications we distinguish histone methylation.

Consequences of histone methylation

• The consequence of the modification is different depending on the targeted residue, its position, etc.

• Concerning histone methylation, they affect all histones but more particularly histones 3 and 4 and most often on arginine and lysine residues.

• When the methylation occurs on histones H3K4, H3K36 and H3K79 we speak of active transcription ; whereas if the methylation affects histones H3K9, H3K27 and H4K20 we speak here of repressed transcription.

Methylation reaction

Methylation is therefore the transfer of a methyl group from a molecule of S-adenosine-methionine (SAM) which is the cofactor, on the side chains therefore at the level of the NH2-terminal domain

Histone methylation as a therapeutic target

• Numerous studies have demonstrated deregulation of histone methylation profiles in various pathologies such as cancers, neurodegenerative diseases, metabolic disorders or autoimmune diseases.

• In cancers in particular, a global loss of H4K20 and H4K16 trimethylation, as well as a gain of H3K27 trimethylation, is frequently observed, contributing to the repression of tumor

suppressor genes.

• Targeting enzymes regulating histone methylation, histone methyltransferases (HMT) represents a promising therapeutic strategy.

CONCLUSION

In conclusion, the state of the chromatin is important, because it regulates the conformation of the DNA and what will allow or not accessibility to the genome, among other things the expression of genes. Thus histones signal the compaction/decompaction of the chromatin fiber through modifications such as methylation.