BRD4 (bromodomain containing 4)

2007-02-01   Anna Collin  

Department of Clinical Genetics, University Hospital, SE-221 85 Lund, Sweden

Identity

HGNC
LOCATION
19p13.12
LOCUSID
ALIAS
CAP,HUNK1,HUNKI,MCAP
FUSION GENES

DNA/RNA

Description

The gene consists of 20 exons that span approximately 43 kb of genomic DNA in the centromere-to-telomere orientation. The translation initiation codon and stop codon are located to exon 2 and exon 20, respectively.

Transcription

Two isoforms of BRD4 have been reported. The "BRD4 long isoform" corresponds to the ordinary full length transcript while the "BRD4 short isoform" corresponds to an alternative splicing variant lacking exons 12-20. The "BRD4 long variant" encodes a 6.0 kb transcript and the "BRD4 short variant" encodes a 4.4 kb transcript.

Proteins

Description

BRD4 belongs to the BET subgroup of the bromodomain superfamily and contains 2 bromodomains and a conserved ET-domain.
The open reading frame encodes a 1362 amino acid protein with a molecular weight of 200 kDa.

Expression

Northen blot analysis has shown an ubiquitous normal expression of both BRD4 isoforms.

Localisation

Nuclear.

Function

A striking feature of BRD4 is its association with euchromatic regions of mitotic chromosomes. By this association, the protein exerts its function as regulator of cell cycle progression from G2 to M but also in the G1 to S transition. It has also been suggested that the association of BRD4 to chromatin is important for the transmission of a transcriptional memory during cell division.

Implicated in

Entity name
Carcinoma with t(15;19)(q14;p13) translocation.
Prognosis
Carcinoma with t(15;19) translocation is invariably fatal with a rapid clinical course when located to the midline thoracic, head and neck structures. One tumor, displaying the cytogenetic and molecular cytogenetic features of carcinoma with t(15;19) translocation, but located to the iliac bone, has been reported as successfully cured.
Cytogenetics
t(15;19)(q14;p13) [reported breakpoints: t(15;19)(q11-15;p13)].
Hybrid gene
The t(15;19)(q14;p13) results in a BRD4-NUT chimeric gene where exon 10 of BRD4 is fused to exon 2 of NUT.
Fusion protein
The BRD4-NUT fusion protein is composed of the N-terminal of BRD4 (amino acids 1-720 out of 1372) and almost the entire protein sequence of NUT (amino acids 6-1127). The N-terminal of BRD4 includes bromodomains 1 and 2 and other, less well characterized functional domains.
Oncogenesis
It has been suggested that the oncogenic effect of the NUT-BRD4 fusion is caused not only by the abnormal regulation of NUT by BRD4 promoter elements but also by the consequent ectopic expression of NUT in non-germinal tissues.

Breakpoints

Note

The vast majority of reported 19p breakpoints were assigned to band 19p13, the exception being the cytogenetic interpretation of a 19q13 breakpoint reported once. The reported breakpoints on chromosome 15 have varied (15q11-q15).

Article Bibliography

Pubmed IDLast YearTitleAuthors

Other Information

Locus ID:

NCBI: 23476
MIM: 608749
HGNC: 13575
Ensembl: ENSG00000141867

Variants:

dbSNP: 23476
ClinVar: 23476
TCGA: ENSG00000141867
COSMIC: BRD4

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000141867ENST00000263377O60885
ENSG00000141867ENST00000360016O60885
ENSG00000141867ENST00000360016A0A024R7H8
ENSG00000141867ENST00000371835O60885
ENSG00000141867ENST00000594841M0QZD9
ENSG00000141867ENST00000597315M0QYW0
ENSG00000141867ENST00000601941M0R0H4
ENSG00000141867ENST00000630599M0QYW0

Expression (GTEx)

0
5
10
15
20
25
30
35
40

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
371204952024LncRNA GAS5 regulated by FTO-mediated m6A demethylation promotes autophagic cell death in NSCLC by targeting UPF1/BRD4 axis.4
372826422024Overexpression of BRD4 in Gastric Cancer and its Clinical Significance as a Novel Therapeutic Target.1
376152182024Transcriptional factor BRD4 promotes the stemness of esophageal cancer by activating the nuclear PD-L1/RelB axis.0
382857602024KDM5C-Mediated Recruitment of BRD4 to Chromatin Regulates Enhancer Activation and BET Inhibitor Sensitivity.0
383095052024The P53-P21-RB1 pathway promotes BRD4 degradation in liver cancer through USP1.0
383307422024Apoptotic body-inspired nanotherapeutics efficiently attenuate osteoarthritis by targeting BRD4-regulated synovial macrophage polarization.0
385001812024Molecular and clinicopathologic characteristics of CNS embryonal tumors with BRD4::LEUTX fusion.1
386011572024Cooperative interaction of interferon regulatory factor -1 and bromodomain-containing protein 4 on RNA polymerase activation for intrinsic innate immunity.0
386488942024High-altitude hypoxia promotes BRD4-mediated activation of the Wnt/β-catenin pathway and disruption of intestinal barrier.0
371204952024LncRNA GAS5 regulated by FTO-mediated m6A demethylation promotes autophagic cell death in NSCLC by targeting UPF1/BRD4 axis.4
372826422024Overexpression of BRD4 in Gastric Cancer and its Clinical Significance as a Novel Therapeutic Target.1
376152182024Transcriptional factor BRD4 promotes the stemness of esophageal cancer by activating the nuclear PD-L1/RelB axis.0
382857602024KDM5C-Mediated Recruitment of BRD4 to Chromatin Regulates Enhancer Activation and BET Inhibitor Sensitivity.0
383095052024The P53-P21-RB1 pathway promotes BRD4 degradation in liver cancer through USP1.0
383307422024Apoptotic body-inspired nanotherapeutics efficiently attenuate osteoarthritis by targeting BRD4-regulated synovial macrophage polarization.0

Citation

Anna Collin

BRD4 (bromodomain containing 4)

Atlas Genet Cytogenet Oncol Haematol. 2007-02-01

Online version: http://atlasgeneticsoncology.org/gene/837/favicon/js/meetings/