BRDT explained

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.^[1]

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.^[2]

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.^{[2] [3]}

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.^[4] 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.^{[2] [3]} As BET inhibitors also inhibit other BET proteins BRD2, BRD3, and BRD4, they are likely to have effects in people beyond temporary male sterility.

Further reading

• Zheng Y, Yuan W, Zhou Z . Molecular cloning and expression of a novel alternative splice variant of BRDT gene. . Int. J. Mol. Med. . 15 . 2 . 315–21 . 2005 . 15647849 . 10.3892/ijmm.15.2.315. etal.
• Gerhard DS, Wagner L, Feingold EA . The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC) . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 . etal.
• Pivot-Pajot C, Caron C, Govin J . Acetylation-Dependent Chromatin Reorganization by BRDT, a Testis-Specific Bromodomain-Containing Protein . Mol. Cell. Biol. . 23 . 15 . 5354–65 . 2003 . 12861021 . 10.1128/MCB.23.15.5354-5365.2003 . 165724 . etal.
• Strausberg RL, Feingold EA, Grouse LH . 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 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . etal. free .
• Hartley JL, Temple GF, Brasch MA . DNA Cloning Using In Vitro Site-Specific Recombination . Genome Res. . 10 . 11 . 1788–95 . 2001 . 11076863 . 10.1101/gr.143000 . 310948 .
• Scanlan MJ, Altorki NK, Gure AO . 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 . 2000 . 10704737 . 10.1016/S0304-3835(99)00385-7 . etal.
• Dhalluin C, Carlson JE, Zeng L . Structure and ligand of a histone acetyltransferase bromodomain . Nature . 399 . 6735 . 491–6 . 1999 . 10365964 . 10.1038/20974 . 1999Natur.399..491D . 1210925 . etal.

Notes and References

1. Jones MH, Numata M, Shimane M . Identification and characterization of BRDT: A testis-specific gene related to the bromodomain genes RING3 and Drosophila fsh . Genomics . 45 . 3 . 529–34 . Jan 1998 . 9367677 . 10.1006/geno.1997.5000 .
2. Web site: Entrez Gene: BRDT bromodomain, testis-specific.
3. 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 . Bromodomain-dependent stage-specific male genome programming by Brdt . EMBO J. 2012 . 22922464 . 10.1038/emboj.2012.233 . 31 . 19 . 3809–20. 3463845 .
4. Web site: A male contraceptive pill in the making?. 16 August 2012. 17 August 2012.