BRD4 (bromodomain containing 4)
2007-02-01 Anna Collin   AffiliationDepartment 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.
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 ID | Last Year | Title | Authors |
|---|---|---|---|
| 12840145 | 2003 | The double bromodomain protein Brd4 binds to acetylated chromatin during interphase and mitosis. | Dey A et al |
| 10938129 | 2000 | A bromodomain protein, MCAP, associates with mitotic chromosomes and affects G(2)-to-M transition. | Dey A et al |
| 16542442 | 2006 | Midline carcinoma with t(15;19) and BRD4-NUT fusion oncogene in a 30-year-old female with response to docetaxel and radiotherapy. | Engleson J et al |
| 11487468 | 2001 | You bet-cha: a novel family of transcriptional regulators. | Florence B et al |
| 15483023 | 2004 | Midline carcinoma of children and young adults with NUT rearrangement. | French CA et al |
| 12543779 | 2003 | BRD4-NUT fusion oncogene: a novel mechanism in aggressive carcinoma. | French CA et al |
| 1785673 | 1991 | Intrathoracic carcinoma in an 11-year-old girl showing a translocation t(15;19). | Kees UR et al |
| 12192049 | 2002 | A Mammalian bromodomain protein, brd4, interacts with replication factor C and inhibits progression to S phase. | Maruyama T et al |
| 16435379 | 2007 | Successful treatment of a child with t(15;19)-positive tumor. | Mertens F et al |
| 15109495 | 2004 | Interaction of the bovine papillomavirus E2 protein with Brd4 tethers the viral DNA to host mitotic chromosomes. | You J et al |
Other Information
Locus ID:
NCBI: 23476
MIM: 608749
HGNC: 13575
Ensembl: ENSG00000141867
Variants:
dbSNP: 23476
ClinVar: 23476
TCGA: ENSG00000141867
COSMIC: BRD4
RNA/Proteins
Expression (GTEx)
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 37120495 | 2024 | LncRNA GAS5 regulated by FTO-mediated m6A demethylation promotes autophagic cell death in NSCLC by targeting UPF1/BRD4 axis. | 4 |
| 37282642 | 2024 | Overexpression of BRD4 in Gastric Cancer and its Clinical Significance as a Novel Therapeutic Target. | 1 |
| 37615218 | 2024 | Transcriptional factor BRD4 promotes the stemness of esophageal cancer by activating the nuclear PD-L1/RelB axis. | 0 |
| 38285760 | 2024 | KDM5C-Mediated Recruitment of BRD4 to Chromatin Regulates Enhancer Activation and BET Inhibitor Sensitivity. | 0 |
| 38309505 | 2024 | The P53-P21-RB1 pathway promotes BRD4 degradation in liver cancer through USP1. | 0 |
| 38330742 | 2024 | Apoptotic body-inspired nanotherapeutics efficiently attenuate osteoarthritis by targeting BRD4-regulated synovial macrophage polarization. | 0 |
| 38500181 | 2024 | Molecular and clinicopathologic characteristics of CNS embryonal tumors with BRD4::LEUTX fusion. | 1 |
| 38601157 | 2024 | Cooperative interaction of interferon regulatory factor -1 and bromodomain-containing protein 4 on RNA polymerase activation for intrinsic innate immunity. | 0 |
| 38648894 | 2024 | High-altitude hypoxia promotes BRD4-mediated activation of the Wnt/β-catenin pathway and disruption of intestinal barrier. | 0 |
| 37120495 | 2024 | LncRNA GAS5 regulated by FTO-mediated m6A demethylation promotes autophagic cell death in NSCLC by targeting UPF1/BRD4 axis. | 4 |
| 37282642 | 2024 | Overexpression of BRD4 in Gastric Cancer and its Clinical Significance as a Novel Therapeutic Target. | 1 |
| 37615218 | 2024 | Transcriptional factor BRD4 promotes the stemness of esophageal cancer by activating the nuclear PD-L1/RelB axis. | 0 |
| 38285760 | 2024 | KDM5C-Mediated Recruitment of BRD4 to Chromatin Regulates Enhancer Activation and BET Inhibitor Sensitivity. | 0 |
| 38309505 | 2024 | The P53-P21-RB1 pathway promotes BRD4 degradation in liver cancer through USP1. | 0 |
| 38330742 | 2024 | Apoptotic 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
