A bromodomain is an approximately 110 amino acid protein domain that recognizes acetylated lysine residues, such as those on the N-terminal tails of . Bromodomains, as the "readers" of lysine acetylation, are responsible in transducing the signal carried by acetylated lysine residues and translating it into various normal or abnormal phenotypes.
Discovery
The bromodomain was identified as a novel
structural motif by John W. Tamkun and colleagues studying the
Drosophila gene
Brahma/
brm, and showed sequence similarity to genes involved in transcriptional activation.
The name "bromodomain" is derived from the relationship of this domain with
Brahma and is unrelated to the chemical element
bromine.
Bromodomain-containing proteins
Bromodomain-containing proteins can have a wide variety of functions, ranging from histone acetyltransferase activity and chromatin remodeling to transcriptional mediation and co-activation. Of the 43 known in 2015, 11 had two bromodomains, and one protein had 6 bromodomains.
Preparation, biochemical analysis, and structure determination of the bromodomain containing proteins have been described in detail.
Bromo- and Extra-Terminal domain (BET) family
A well-known example of a bromodomain family is the BET (Bromodomain and extraterminal domain) family. Members of this family include BRD2, BRD3, BRD4 and
BRDT.
Other
However proteins such as ASH1L also contain a bromodomain. Dysfunction of BRD proteins has been linked to diseases such as human squamous cell carcinoma and other forms of cancer.
Histone acetyltransferases, including EP300 and
PCAF, have bromodomains in addition to acetyl-transferase domains.
Not considered part of the BET family (yet containing a bromodomain) are BRD7, and BRD9.
Role in human disease
The role of bromodomains in translating a deregulated cell acetylome into disease phenotypes was recently unveiled by the development of small molecule bromodomain inhibitors. This breakthrough discovery highlighted bromodomain-containing proteins as key players in cancer biology, as well as inflammation
and
remyelination in multiple sclerosis.
Members of the BET family have been implicated as targets in both human cancer
Small molecule inhibitors of non-BET bromodomain proteins BRD7 and BRD9 have also been developed.
See also
