| Written | 2007-02 | Anna Collin |
| Department of Clinical Genetics, University Hospital, SE-221 85 Lund, Sweden |
| Identity |
| Alias_names | bromodomain-containing 4 |
| Alias_symbol (synonym) | HUNKI |
| MCAP | |
| CAP | |
| HUNK1 | |
| Other alias | |
| HGNC (Hugo) | BRD4 |
| LocusID (NCBI) | 23476 |
| Atlas_Id | 837 |
| Location | 19p13.12 [Link to chromosome band 19p13] |
| Location_base_pair | Starts at 15252995 and ends at 15332543 bp from pter ( according to hg19-Feb_2009) [Mapping BRD4.png] |
| Fusion genes (updated 2017) | Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands) |
| BRD4 (19p13.12) / BRD4 (19p13.12) | BRD4 (19p13.12) / NUTM1 (15q14) | CD99L2 (Xq28) / BRD4 (19p13.12) | |
| NUTM1 (15q14) / BRD4 (19p13.12) | RARA (17q21.2) / BRD4 (19p13.12) | ||
| 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. |
| Protein |
| 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 |
| Note | |
| Entity | 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/Mutated 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. |
| Abnormal 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). |
| Bibliography |
| The double bromodomain protein Brd4 binds to acetylated chromatin during interphase and mitosis. |
| Dey A, Chitsaz F, Abbasi A, Misteli T, Ozato K |
| Proceedings of the National Academy of Sciences of the United States of America. 2003 ; 100 (15) : 8758-8763. |
| PMID 12840145 |
| A bromodomain protein, MCAP, associates with mitotic chromosomes and affects G(2)-to-M transition. |
| Dey A, Ellenberg J, Farina A, Coleman AE, Maruyama T, Sciortino S, Lippincott-Schwartz J, Ozato K |
| Molecular and cellular biology. 2000 ; 20 (17) : 6537-6549. |
| PMID 10938129 |
| 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, Soller M, Panagopoulos I, Dahlén A, Dictor M, Jerkeman M |
| BMC cancer. 2006 ; 6 : page 69. |
| PMID 16542442 |
| You bet-cha: a novel family of transcriptional regulators. |
| Florence B, Faller DV |
| Frontiers in bioscience : a journal and virtual library. 2001 ; 6 : D1008-D1018. |
| PMID 11487468 |
| Midline carcinoma of children and young adults with NUT rearrangement. |
| French CA, Kutok JL, Faquin WC, Toretsky JA, Antonescu CR, Griffin CA, Nose V, Vargas SO, Moschovi M, Tzortzatou-Stathopoulou F, Miyoshi I, Perez-Atayde AR, Aster JC, Fletcher JA |
| Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2004 ; 22 (20) : 4135-4139. |
| PMID 15483023 |
| BRD4-NUT fusion oncogene: a novel mechanism in aggressive carcinoma. |
| French CA, Miyoshi I, Kubonishi I, Grier HE, Perez-Atayde AR, Fletcher JA |
| Cancer research. 2003 ; 63 (2) : 304-307. |
| PMID 12543779 |
| Intrathoracic carcinoma in an 11-year-old girl showing a translocation t(15;19). |
| Kees UR, Mulcahy MT, Willoughby ML |
| The American journal of pediatric hematology/oncology. 1991 ; 13 (4) : 459-464. |
| PMID 1785673 |
| A Mammalian bromodomain protein, brd4, interacts with replication factor C and inhibits progression to S phase. |
| Maruyama T, Farina A, Dey A, Cheong J, Bermudez VP, Tamura T, Sciortino S, Shuman J, Hurwitz J, Ozato K |
| Molecular and cellular biology. 2002 ; 22 (18) : 6509-6520. |
| PMID 12192049 |
| Carcinoma with t(15;19) translocation. |
| Marx A, French CA, Fletcher JA |
| In.. |
| Successful treatment of a child with t(15;19)-positive tumor. |
| Mertens F, Wiebe T, Adlercreutz C, Mandahl N, French CA |
| Pediatric blood & cancer. 2007 ; 49 (7) : 1015-1017. |
| PMID 16435379 |
| Interaction of the bovine papillomavirus E2 protein with Brd4 tethers the viral DNA to host mitotic chromosomes. |
| You J, Croyle JL, Nishimura A, Ozato K, Howley PM |
| Cell. 2004 ; 117 (3) : 349-360. |
| PMID 15109495 |
| Citation |
| This paper should be referenced as such : |
| Collin, A |
| BRD4 (bromodomain containing 4) |
| Atlas Genet Cytogenet Oncol Haematol. 2007;11(3):180-181. |
| Free journal version : [ pdf ] [ DOI ] |
| On line version : http://AtlasGeneticsOncology.org/Genes/BRD4ID837ch19p13.html |
| Other Leukemias implicated (Data extracted from papers in the Atlas) [ 1 ] |
|
t(14;19)(q32;p13) IGH/EPOR::t(14;19)(q32;p13) IGH/BRD4 ?
|
| Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 1 ] |
|
Midline Carcinoma: t(15;19)(q14;p13) BRD4/NUTM1
|
| External links |
| REVIEW articles | automatic search in PubMed |
| Last year publications | automatic search in PubMed |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Thu Oct 12 16:17:35 CEST 2017 |
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