BRDT

BRDT
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
Aliases BRDT, BRD6, CT9, bromodomain testis associated
External IDs MGI: 1891374 HomoloGene: 21064 GeneCards: BRDT
Targeted by Drug
jq1[1]
Orthologs
Species Human Mouse
Entrez

676

114642

Ensembl

ENSG00000137948

ENSMUSG00000029279

UniProt

Q58F21

Q91Y44

RefSeq (mRNA)

NM_001079873
NM_054054

RefSeq (protein)

NP_001073342.1
NP_473395.2

Location (UCSC) Chr 1: 91.95 – 92.01 Mb Chr 5: 107.33 – 107.39 Mb
PubMed search [2] [3]
Wikidata
View/Edit HumanView/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.[4][5]

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.[5] 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.[5][6]

Model organisms

Model organisms have been used in the study of BRDT function. A conditional knockout mouse line, called Brdttm1a(EUCOMM)Wtsi[12][13] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[14][15][16]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[10][17] Twenty five tests were carried out on mutant mice and two significant abnormalities were observed.[10] Homozygous mutant males were sub-fertile and both sexes had a decreased number of lumbar and sacral vertebrae.[10]

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.[18] 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.[5][6] 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. "Drugs that physically interact with Bromodomain testis-specific protein view/edit references on wikidata".
  2. "Human PubMed Reference:".
  3. "Mouse PubMed Reference:".
  4. 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.
  5. 1 2 3 4 "Entrez Gene: BRDT bromodomain, testis-specific".
  6. 1 2 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. PMID 22922464.
  7. "Radiography data for Brdt". Wellcome Trust Sanger Institute.
  8. "Salmonella infection data for Brdt". Wellcome Trust Sanger Institute.
  9. "Citrobacter infection data for Brdt". Wellcome Trust Sanger Institute.
  10. 1 2 3 4 Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
  11. Mouse Resources Portal, Wellcome Trust Sanger Institute.
  12. "International Knockout Mouse Consortium".
  13. "Mouse Genome Informatics".
  14. Skarnes, W. C.; Rosen, B.; West, A. P.; Koutsourakis, M.; Bushell, W.; Iyer, V.; Mujica, A. O.; Thomas, M.; Harrow, J.; Cox, T.; Jackson, D.; Severin, J.; Biggs, P.; Fu, J.; Nefedov, M.; De Jong, P. J.; Stewart, A. F.; Bradley, A. (2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–342. doi:10.1038/nature10163. PMC 3572410Freely accessible. PMID 21677750.
  15. Dolgin E (2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
  16. Collins FS, Rossant J, Wurst W (2007). "A Mouse for All Reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
  17. van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism.". Genome Biol. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837Freely accessible. PMID 21722353.
  18. "A male contraceptive pill in the making?". 16 August 2012. Retrieved 17 August 2012.

Further reading

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