Entry - *601541 - BROMODOMAIN-CONTAINING PROTEIN 3; BRD3 - OMIM
 
* 601541

BROMODOMAIN-CONTAINING PROTEIN 3; BRD3


Alternative titles; symbols

RING3-LIKE GENE; RING3L
OPEN READING FRAME X; ORFX


HGNC Approved Gene Symbol: BRD3

Cytogenetic location: 9q34.2     Genomic coordinates (GRCh38): 9:134,030,305-134,068,548 (from NCBI)


TEXT

Cloning and Expression

Nomura et al. (1994) identified ORFX as a non-linked copy of RING3 (BRD2; 601540), a gene in the human major histocompatibility complex (MHC) class II region on 6p21.3.


Mapping

Using a PCR probe derived from the ORFX cDNA sequence, Thorpe et al. (1996) mapped the gene, symbolized here RING3L, by fluorescence in situ hybridization analysis to 9q34. Several other MHC-related genes have been found to map to the same region.


Gene Function

Dawson et al. (2011) demonstrated that I-BET151, a novel small molecule inhibitor of the BET family, of which BRD3 is a member, has profound efficacy against human and murine MLL-fusion leukemia cell lines through the induction of early cell cycle arrest and apoptosis. I-BET151 treatment in 2 human leukemia cell lines with different MLL fusions altered the expression of a common set of genes whose function may account for these phenotypic changes. The mode of action of I-BET151 is, at least in part, due to the inhibition of transcription at key genes BCL2 (151430), C-MYC (190080), and CDK6 (603368) through the displacement of BRD3/4, PAFc, and SEC components from chromatin. In vivo studies indicated that I-BET151 has significant therapeutic value, providing survival benefit in 2 distinct mouse models of murine


REFERENCES

  1. Dawson, M. A., Prinjha, R. K., Dittmann, A., Giotopoulos, G., Bantscheff, M., Chan, W.-I., Robson, S. C., Chung, C., Hopf, C., Savitski, M. M., Huthmacher, C., Gudgin, E., and 15 others. Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. Nature 478: 529-533, 2011. [PubMed: 21964340, images, related citations] [Full Text]

  2. Nomura, N., Nagase, T., Miyajima, N., Sazuka, T., Tanaka, A., Sato, S., Seki, N., Kawarabayasi, Y., Ishikawa, K., Tabata, S. Prediction of the coding sequences of unidentified human genes. II. The coding sequences of 40 new genes (KIAA0041-KIAA0080) deduced by analysis of cDNA clones from human cell line KG-1. DNA Res. 1: 223-229, 1994. [PubMed: 7584044, related citations] [Full Text]

  3. Thorpe, K. L., Abdulla, S., Kaufman, J., Trowsdale, J., Beck, S. Phylogeny and structure of the RING3 gene. Immunogenetics 44: 391-396, 1996. [PubMed: 8781126, related citations] [Full Text]


Contributors:
Ada Hamosh - updated : 1/4/2012
Creation Date:
Victor A. McKusick : 11/27/1996
alopez : 01/06/2012
terry : 1/4/2012
alopez : 1/6/2005
mgross : 7/24/2000
alopez : 6/27/1997
mark : 11/27/1996

* 601541

BROMODOMAIN-CONTAINING PROTEIN 3; BRD3


Alternative titles; symbols

RING3-LIKE GENE; RING3L
OPEN READING FRAME X; ORFX


HGNC Approved Gene Symbol: BRD3

Cytogenetic location: 9q34.2     Genomic coordinates (GRCh38): 9:134,030,305-134,068,548 (from NCBI)


TEXT

Cloning and Expression

Nomura et al. (1994) identified ORFX as a non-linked copy of RING3 (BRD2; 601540), a gene in the human major histocompatibility complex (MHC) class II region on 6p21.3.


Mapping

Using a PCR probe derived from the ORFX cDNA sequence, Thorpe et al. (1996) mapped the gene, symbolized here RING3L, by fluorescence in situ hybridization analysis to 9q34. Several other MHC-related genes have been found to map to the same region.


Gene Function

Dawson et al. (2011) demonstrated that I-BET151, a novel small molecule inhibitor of the BET family, of which BRD3 is a member, has profound efficacy against human and murine MLL-fusion leukemia cell lines through the induction of early cell cycle arrest and apoptosis. I-BET151 treatment in 2 human leukemia cell lines with different MLL fusions altered the expression of a common set of genes whose function may account for these phenotypic changes. The mode of action of I-BET151 is, at least in part, due to the inhibition of transcription at key genes BCL2 (151430), C-MYC (190080), and CDK6 (603368) through the displacement of BRD3/4, PAFc, and SEC components from chromatin. In vivo studies indicated that I-BET151 has significant therapeutic value, providing survival benefit in 2 distinct mouse models of murine


REFERENCES

  1. Dawson, M. A., Prinjha, R. K., Dittmann, A., Giotopoulos, G., Bantscheff, M., Chan, W.-I., Robson, S. C., Chung, C., Hopf, C., Savitski, M. M., Huthmacher, C., Gudgin, E., and 15 others. Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. Nature 478: 529-533, 2011. [PubMed: 21964340] [Full Text: https://doi.org/10.1038/nature10509]

  2. Nomura, N., Nagase, T., Miyajima, N., Sazuka, T., Tanaka, A., Sato, S., Seki, N., Kawarabayasi, Y., Ishikawa, K., Tabata, S. Prediction of the coding sequences of unidentified human genes. II. The coding sequences of 40 new genes (KIAA0041-KIAA0080) deduced by analysis of cDNA clones from human cell line KG-1. DNA Res. 1: 223-229, 1994. [PubMed: 7584044] [Full Text: https://doi.org/10.1093/dnares/1.5.223]

  3. Thorpe, K. L., Abdulla, S., Kaufman, J., Trowsdale, J., Beck, S. Phylogeny and structure of the RING3 gene. Immunogenetics 44: 391-396, 1996. [PubMed: 8781126] [Full Text: https://doi.org/10.1007/BF02602785]


Contributors:
Ada Hamosh - updated : 1/4/2012

Creation Date:
Victor A. McKusick : 11/27/1996

Edit History:
alopez : 01/06/2012
terry : 1/4/2012
alopez : 1/6/2005
mgross : 7/24/2000
alopez : 6/27/1997
mark : 11/27/1996