CHROMODOMAIN AND BROMODOMAIN

 Chromodomain

A chromodomain is a protein structural domain of around 40-50 amino acid residues that is frequently found in proteins involved in chromatin remodelling and manipulation. Additionally, it is referred to as a chromatin organisation modifier. It was discovered for the first time in Drosophila moderators of variegation.The chromodomains remodel chromatin into the condensed shape of heterochromatin, a cytologically observable state of suppressed gene expression.Both plants and animals have a high degree of conservation within the domain.It is encoded by a huge number of proteins found in a wide variety of genomes.Certain genes with chromodomains have several alternative splicing isoforms that lack the chromodomain altogether.Chromodomain-containing proteins are involved in many aspects of gene regulation in mammals, including chromatin remodelling and the development of heterochromatin areas. Additionally, proteins with chromodomains bind methylated histones and are included in the RNA-induced transcriptional silencing complex.

Proteins with a chromo domain tend to fall into three categories.

(i)The first class of proteins comprises those with an N-terminal chromo domain followed by a region referred to as the chromo shadow domain that has just a passing resemblance to the N-terminal chromo domain, such as the Drosophila and human heterochromatin protein Su(var)205 (HP1).

(ii) The second class of proteins comprises those with a single chromodomain, such as Polycomb (Pc) protein from Drosophila; mammalian modifier 3; human Mi-2 autoantigen; and various putative proteins from yeast and Caenorhabditis elegans.

(iii) The third type has paired tandem chromodomains, such as those seen in human DNA-binding/helicase proteins CHD-1 through CHD-4 and yeast protein CHD1.

Functional dissections of chromodomain proteins reveal that chromo domains have a molecular function in directing chromodomain proteins to certain nucleosome locations. Protein-protein and/or protein-nucleic acid interactions may be involved in the targeting process.

Bromodomain

Bromodomains (BRD) are tiny nuclear proteins that bind specifically to histone proteins' acetylated lysine residues. Once attached, these BRDs recruit complexes of proteins involved in chromatin structure control, hence regulating gene expression. A bromodomain is a protein domain containing roughly 110 amino acids that detects acetylated lysine residues.Bromodomains act as "readers" of lysine acetylation, converting the signal delivered by acetylated lysine residues into a variety of normal or aberrant phenotypes.

Their affinity is greater for areas with several acetylation sites located close together.This recognition is often required for the binding of proteins to histones and chromatin remodelling. The domain adopts an all-protein shape, consisting of a bundle of four alpha helices separated by variable length loop sections that create a hydrophobic pocket that binds acetyl lysine.John W. Tamkun and colleagues discovered the bromodomain as a unique structural motif while examining the drosophila gene Brahma/brm, and demonstrated sequence similarities to genes involved in transcriptional activation.The term "bromodomain" is derived from the domain's link with Brahma and has nothing to do with the actual element bromine.

Bromodomain-containing proteins may perform a broad range of tasks, including histone acetyltransferase activity and chromatin remodelling, as well as transcriptional mediation and co-activation.

The BET family is a well-known example of a bromodomain family (Bromodomain and extraterminal domain family). BRD2, BRD3, BRD4, and BRDT are all members of this family. However, several proteins, such as ASH1L, include a bromodomain as well. BRD protein dysfunction has been associated to human squamous cell carcinoma and other types of cancer.

Bromodomains' significance in translating a dysregulated cell acetylome into disease phenotypes was recently shown via the creation of small chemical bromodomain inhibitors. This ground-breaking finding established bromodomain-containing proteins as critical components of cancer biology, as well as inflammation and remyelination in multiple sclerosis. Bromodomain-containing proteins also influence the change of juvenile to mature leaf morphology in plants.