BRDT
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesBRDT, BRD6, CT9, bromodomain testis associated, SPGF21
External IDsOMIM: 602144 MGI: 1891374 HomoloGene: 21064 GeneCards: BRDT
Orthologs
SpeciesHumanMouse
Entrez

676

114642

Ensembl

ENSG00000137948

ENSMUSG00000029279

UniProt

Q58F21

Q91Y44

RefSeq (mRNA)

NM_001079873
NM_054054

RefSeq (protein)

NP_001073342
NP_473395

Location (UCSC)Chr 1: 91.95 – 92.01 MbChr 5: 107.33 – 107.39 Mb
PubMed search[3][4]
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.[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. 1 2 3 GRCh38: Ensembl release 89: ENSG00000137948 - Ensembl, May 2017
  2. 1 2 3 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. 1 2 3 4 "Entrez Gene: BRDT bromodomain, testis-specific".
  7. 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. PMC 3463845. PMID 22922464.
  8. "A male contraceptive pill in the making?". 16 August 2012. Retrieved 17 August 2012.

Further reading

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