Epigenetics

Epigenetics is the study of heritable changes in gene expression that are stable between cell divisions, and sometimes between generations without changing the nucleotide sequence. There are many epigenetic phenomena, such as DNA methylation, genomic imprinting, maternal effects, gene silencing, dominant nucleoli, dormant transposons activation and RNA editing.

Chromatin remodelers are multi-protein complexes that use the energy of ATP hydrolysis, in order to slide, exchange or remove nucleosomes. Chromatin remodelers make promoter and enhancer regions either more or less accessible to the transcriptional apparatus, thereby allowing transcription factors to activate or repress, respectively, the transcription of their target genes. Thus, nucleosome occupancy and composition are tailored genome-wide by specialized remodelers.Chromatin remodelers are key players in the regulation of chromatin accessibility and nucleosome positioning on the eukaryotic DNA, thereby essential for all DNA dependent biological processes. Thus, it is not surprising that upon of deregulation of those molecular machines healthy cells can turn into cancerous cells.

DNA methyltransferases (DNMTs),including DNMT1, DNMT3a and DNMT3b, are a family of enzymes that catalyze the addition of methyl groups onto DNA. DNMT1 acts as the primary maintenance methyltransferase to keep the methylation of DNA that is already established at the genome, whereas DNMT3a and DNMT3b are classified asde novo methyltransferases to reversibly methylate unmethylated DNA. The mechanism of action for DNA methyltransferases (DNMTs) involves the transfer of a methyl group from S-adenosyl methionine (SAM) to the target DNA.

DNA methyltransferases (DNMTs)
DNMT1 DNMT3A DNMT3L
FECH MGMT DNMT2

Histones are the chief components of chromatin. When being catalyzed by a series of histone modifying enzymes, histones may undergo various post-translational modifications such as acetylation, methylation, phosphorylation, ubiquitylation and SUMOylation. The dysregulation of histone modifying enzymes will alter the histone post-modification patterns and cause diverse diseases including cancers. Consequently, the histone modifying enzymes have emerged as the promising biomarkers for disease diagnosis and prognosis.

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