BRDT

BRDT
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2RFJ, 4FLP, 4KCX
Identifiers
Aliases	BRDT , BRD6, CT9, bromodomain testis associated, SPGF21
External IDs	OMIM: 602144; MGI: 1891374; HomoloGene: 21064; GeneCards: BRDT; OMA:BRDT - orthologs
Gene location (Human) Chr. Chromosome 1 (human) [1] Band 1p22.1 Start 91,949,343 bp [1] End 92,014,426 bp [1]
Gene location (Mouse) Chr. Chromosome 5 (mouse) [2] Band 5|5 E5 Start 107,331,159 bp [2] End 107,387,058 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in left testis right testis gonad testicle sperm buccal mucosa cell oocyte paraflocculus of cerebellum placenta granulocyte Top expressed in zygote secondary oocyte spermatocyte seminiferous tubule spermatid primary oocyte olfactory epithelium lumbar spinal ganglion Gonadal ridge female urethra More reference expression data BioGPS n/a
Gene ontology Molecular function transcription coactivator activity histone binding lysine-acetylated histone binding Cellular component nucleus Biological process male meiotic nuclear division positive regulation of transcription involved in meiotic cell cycle chromatin remodeling mRNA processing male meiosis I cell differentiation regulation of RNA splicing meiosis transcription, DNA-templated spermatogenesis RNA splicing regulation of transcription, DNA-templated chromatin organization Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 676 114642 Ensembl ENSG00000137948 ENSMUSG00000029279 UniProt Q58F21 Q91Y44 RefSeq (mRNA) NM_001242805 NM_001242806 NM_001242807 NM_001242808 NM_001242810 NM_001726 NM_207189 NM_001079873 NM_054054 RefSeq (protein) NP_001229734 NP_001229735 NP_001229736 NP_001229737 NP_001229739 NP_001717 NP_997072 NP_001073342 NP_473395 Location (UCSC) Chr 1: 91.95 – 92.01 Mb Chr 5: 107.33 – 107.39 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Bromodomain testis-specific protein is a protein that in humans is encoded by the BRDT gene. It is a member of the Bromodomain and Extra-terminal motif (BET) protein family. ^{[5] [6]}

BRDT is similar to the RING3 protein family. It possesses 2 bromodomain motifs and a PEST sequence (a cluster of proline, glutamic acid, serine, and threonine residues), characteristic of proteins that undergo rapid intracellular degradation. The bromodomain is found in proteins that regulate transcription. Two transcript variants encoding the same protein have been found for this gene. ^[6]

The use of three different mouse models (Brdt knock-out mice, mice expressing a non-functional Brdt and mice expressing a mutated Brdt lacking its first bromodomain) showed that Brdt drives a meiotic and post-meiotic gene expression program. It also controls the genome-wide post-meiotic genome reorganization that occurs after histone hyperacetylation in elongating spermatids. ^{[6] [7]}

Potential as target of Male contraceptive medication

BET inhibitors such as JQ1 block the region of BRDT responsible for chromatin binding, and cause a reversible reduction of sperm production, sperm quality, and size of the testis in mice. ^[8] The mechanism of action of JQ1 could be explained by considering Brdt’s functions as a driver of testis-specific gene expression and post-meiotic chromatin reorganization. ^{[6] [7]} As BET inhibitors also inhibit other BET proteins BRD2, BRD3, and BRD4, they are likely to have effects in people beyond temporary male sterility.

References

1. GRCh38: Ensembl release 89: ENSG00000137948 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000029279 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Jones MH, Numata M, Shimane M (Jan 1998). "Identification and characterization of BRDT: A testis-specific gene related to the bromodomain genes RING3 and Drosophila fsh". Genomics. 45 (3): 529–34. doi:10.1006/geno.1997.5000. PMID   9367677.
6. "Entrez Gene: BRDT bromodomain, testis-specific".
7. Gaucher J, Boussouar F, Montellier E, Curtet S, Buchou T, Bertrand S, Hery P, Jounier S, Depaux A, Vitte AL, Guardiola P, Pernet K, Debernardi A, Lopez F, Holota H, Imbert J, Wolgemuth DJ, Gérard M, Rousseaux S, Khochbin S (2012). "Bromodomain-dependent stage-specific male genome programming by Brdt". EMBO J. 31 (19): 3809–20. doi:10.1038/emboj.2012.233. PMC   3463845 . PMID   22922464.
8. "A male contraceptive pill in the making?". 16 August 2012. Retrieved 17 August 2012.

External links

• Human BRDT genome location and BRDT gene details page in the UCSC Genome Browser .

Further reading

• Zheng Y, Yuan W, Zhou Z, et al. (2005). "Molecular cloning and expression of a novel alternative splice variant of BRDT gene". Int. J. Mol. Med. 15 (2): 315–21. doi:10.3892/ijmm.15.2.315. PMID   15647849.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC   528928 . PMID   15489334.
• Pivot-Pajot C, Caron C, Govin J, et al. (2003). "Acetylation-Dependent Chromatin Reorganization by BRDT, a Testis-Specific Bromodomain-Containing Protein". Mol. Cell. Biol. 23 (15): 5354–65. doi:10.1128/MCB.23.15.5354-5365.2003. PMC   165724 . PMID   12861021.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi: 10.1073/pnas.242603899 . PMC   139241 . PMID   12477932.
• Hartley JL, Temple GF, Brasch MA (2001). "DNA Cloning Using In Vitro Site-Specific Recombination". Genome Res. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC   310948 . PMID   11076863.
• Scanlan MJ, Altorki NK, Gure AO, et al. (2000). "Expression of cancer-testis antigens in lung cancer: definition of bromodomain testis-specific gene (BRDT) as a new CT gene, CT9". Cancer Lett. 150 (2): 155–64. doi:10.1016/S0304-3835(99)00385-7. PMID   10704737.
• Dhalluin C, Carlson JE, Zeng L, et al. (1999). "Structure and ligand of a histone acetyltransferase bromodomain". Nature. 399 (6735): 491–6. Bibcode:1999Natur.399..491D. doi:10.1038/20974. PMID   10365964. S2CID   1210925.