Studying Bromodomain Containing Proteins with knock out cell lines

What Is A Bromodomain?

Definition: The bromodomain is a 110 amino acid protein domain that can recognise monoacetylated lysine residues. The recognition is a pre-requisite for chromatin remodelling and BRD containing proteins play an important role in directing chromatin remodelling enzymes to specific sites.

Overview of bromodomain containing proteins

Bromodomains work in parallel with other protein modules in order to give a high level of specificity. BRD containing proteins can have single or multiple BRD domains. A well-known example of a BRD containing protein complexes are the SWI/SNF complexes, the composition of which determines whether the complex activates or represses gene transcription.

Bromodomain related diseases explored with gene edited cell lines

A number of proteins that use BRDs for their recruitment to specific regulatory complexes have been implicated in the development of cancer; in addition gene re-arrangements and overexpression of BRD containing genes have been reported in a number of cancers. For example, a functional association between SW1/SNF and the response of a chemotherapy compound, docetaxal, was confirmed in HAP1 cell line knockouts Mol Syst Biol. (2016) 12: 879

 BRDs are also attractive targets for neurological and inflammatory diseases. Potent and selective inhibitors to the BET (bromodomain and extraterminal domain) family are being trialled.

Bromodomain diagram

The human genome encodes 42 bromodomain-containing genes, which harbour 52 bromodomains (some genes contain more than one bromodomain).

Please note that several bromodomain-containing proteins contain more than one bromodomain. In that case, bromodomains are numbered (e.g. BRD4_1 and BRD4_2).

Examples of popular knockout cell lines

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