BRDT

Bromodomain, testis-specific
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2RFJ, 4FLP, 4KCX
Identifiers
Symbols	BRDT ; BRD6; CT9
External IDs	OMIM: 602144 MGI: 1891374 HomoloGene: 21064 ChEMBL: 1795185 GeneCards: BRDT Gene
Gene ontology Molecular function • transcription coactivator activity • histone binding • lysine-acetylated histone binding Cellular component • nucleus Biological process • histone displacement • chromatin remodeling • transcription, DNA-templated • mRNA processing • male meiosis • male meiosis I • spermatogenesis • RNA splicing • cell differentiation • regulation of RNA splicing • positive regulation of transcription during meiosis Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	676	114642
Ensembl	ENSG00000137948	ENSMUSG00000029279
UniProt	Q58F21	Q91Y44
RefSeq (mRNA)	NM_001242805	NM_001079873
RefSeq (protein)	NP_001229734	NP_001073342
Location (UCSC)	Chr 1: 91.95 – 92.01 Mb	Chr 5: 107.33 – 107.39 Mb
PubMed search	[1]	[2]

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.

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. 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.

Model organisms

Brdt knockout mouse phenotype

Characteristic	Phenotype
Homozygote viability	Normal
Fertility	Abnormal
Body weight	Normal
Anxiety	Normal
Neurological assessment	Normal
Grip strength	Normal
Hot plate	Normal
Dysmorphology	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Radiography	Abnormal
Body temperature	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Plasma immunoglobulins	Normal
Haematology	Normal
Micronucleus test	Normal
Heart weight	Normal
Tail epidermis wholemount	Normal
Skin Histopathology	Normal
Brain histopathology	Normal
Salmonella infection	Normal
Citrobacter infection	Normal
All tests and analysis from

Model organisms have been used in the study of BRDT function. A conditional knockout mouse line, called Brdt^{tm1a(EUCOMM)Wtsi} 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.

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

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. 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. As BET inhibitors also inhibit other BET proteins BRD2, BRD3, and BRD4, they are likely to have effects in people beyond temporary male sterility.