Writer Enzymes

Chromatin Modifying Enzymes: The Writers Epigenetic regulation of the genome is a critical facet of development. Chromatin accessibility is mainly regulated by chemical modifications of histone proteins & DNA and the recognition of these marks by other proteins and protein complexes. Histone modifications and DNA methylation are often intertwined; each epigenetic signature can influence the other's recruitment to reinforce differential epigenetic states. Writers are the specialized enzymes that catalyze these chemical modifications of histones & DNA e.g. histone methylation, acetylation, phosphorylation, ubiquitination, DNA methylation etc.

DNA methylation catalyzed by DNA methyltransferases (DNMTs) primarily occurs on cytosine residue of CpG dinucleotides & induces transcriptional repression. Different members of the DNMTs act either as de novo DNMTs or as maintenance DNMTs. De novo DNMTs add the initial pattern of methyl groups in place on a DNA sequence & maintenance DNMTs copy the methylation from an existing DNA strand to its new partner after replication. While addition of acetyl group to histones by histone acetyltransferases (HAT) creates an accessible chromatin conformation, histone methylation by Protein lysine methyltransferases (PKMTs) can confer both an active or repressed transcriptional state depending upon which lysine is methylated. Histone 3 lysine 9 (H3K9), histone 4 lysine 20 (H4K20), and histone 3 lysine 27 (H3K27) are silencing modifications, whereas histone 3 lysine 4 (H3K4) methylation produces active chromatin. Similarly histone methylation by Protein arginine methyltransferases (PRMTs) can confer both an active or repressed transcriptional state depending upon the symmetry of the methyl groups added to the arginine residues. Phosphorylation of serine and threonine residues of the histone tails appears to be involved in chromatin condensation during mitosis and meiosis as well as in recruitment of DNA damage repair proteins to DNA double-strand break site. Monoubiquitination of H2A is frequently correlated with gene silencing, while Monoubiquitination of H2B is mostly associated with transcription activation. Given the many chromatin remodeling processes in which writer enzymes play an important part, it is not surprising that deregulation of these enzymes have been linked to various disease syndromes, including cancer.

BioVision offers a broad range of validated writer enzymes & cofactors, enzyme activators & inhibitors, antibodies, blocking peptides & assay kits to study these DNA & histone modifications.

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