Expression of a Testis-Specific Form of Gal3st1 (CST), a Gene Essential for Spermatogenesis, Is Regulated by the CTCF Paralogous Gene BORIS

Suzuki, Tomohiko; Kosaka-Suzuki, Natsuki; Pack, Svetlana D.; Shin, Dong‐Mi; Yoon, Jeongheon; Abdullaev, Ziedulla; Pugacheva, Elena M.; Morse, Herbert C.; Loukinov, Dmitri; Lobanenkov, Victor

doi:10.1128/mcb.01093-09

Cited by 72 publications

(113 citation statements)

References 59 publications

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“…Mice-Boris knock-out mice were generated as described previously (25). All animal experiments were conducted in compliance with the Animal Care and Use Committee of the NIAID, National Institutes of Health.…”

Section: Methodsmentioning

confidence: 99%

“…Purification of Spermatocytes and Round Spermatids-Spermatocytes and round spermatids were purified as previously described (25). Briefly, dissociated testicular cells were separated by centrifugal elutriation.…”

Section: Methodsmentioning

confidence: 99%

“…Antibodies-The antibody against mouse BORIS used for chromatin immunoprecipitation (ChIP) analysis was described previously (25). Mouse monoclonal antibodies specific for human BORIS were produced using recombinant human BORIS protein prepared from larvae of Trichoplusia ni infected with baculovirus expressing full-length human BORIS.…”

Section: Methodsmentioning

confidence: 99%

“…Given the possible utility of TSP50 as a target for tumor immunotherapy, we felt that clarification of the regulatory mechanisms was an important issue. We recently reported that BORIS is involved in regulating Tsp50 expression in testis, although it was not clear whether reduced expression of Tsp50 in testis of Boris knockout (KO) mice was a primary or secondary effect of the loss of BORIS (25).…”

Section: Ctcfmentioning

confidence: 99%

“…BORIS contains an 11ZF domain that is highly similar to the 11ZF domain of CTCF. We recently reported that BORIS plays important physiological functions in progression of spermatogenesis by regulating expression of a testis-specific splicing variant of cerebroside sulfotransferase (Cst), Cst form F TS (25).…”

Section: Ctcfmentioning

confidence: 99%

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Transcription Factor BORIS (Brother of the Regulator of Imprinted Sites) Directly Induces Expression of a Cancer-Testis Antigen, TSP50, through Regulated Binding of BORIS to the Promoter

Kosaka-Suzuki¹,

Suzuki²,

Pugacheva

et al. 2011

Journal of Biological Chemistry

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Cancer-testis antigens (CTAs) are normally expressed in testis but are aberrantly expressed in a variety of cancers with varying frequency. More than 100 proteins have been identified as CTA including testes-specific protease 50 (TSP50) and the testis-specific paralogue of CCCTC-binding factor, BORIS (brother of the regulator of imprinted sites). Because many CTAs are considered as excellent targets for tumor immunotherapy, understanding the regulatory mechanisms governing their expression is important. In this study we demonstrate that BORIS is directly responsible for the transcriptional activation of TSP50. We found two BORIS binding sites in the TSP50 promoter that are highly conserved between mouse and human. Mutations of the binding sites resulted in loss of BORIS binding and the ability of BORIS to activate the promoter. However, although expression of BORIS was essential, it was not sufficient for high expression of TSP50 in cancer cells. Further studies showed that binding of BORIS to the target sites was methylation-independent but was diminished by nucleosomal occupancy consistent with the findings that high expression of TSP50 was associated with increased DNase I sensitivity and high BORIS occupancy of the promoter. These findings indicate that BORIS-induced expression of TSP50 is governed by accessibility and binding of BORIS to the promoter. To our knowledge this is the first report of regulated expression of one CTA by another to be validated in a physiological context.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Ctcfmentioning

confidence: 99%

Section: Ctcfmentioning

confidence: 99%

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Transcription Factor BORIS (Brother of the Regulator of Imprinted Sites) Directly Induces Expression of a Cancer-Testis Antigen, TSP50, through Regulated Binding of BORIS to the Promoter

Kosaka-Suzuki¹,

Suzuki²,

Pugacheva

et al. 2011

Journal of Biological Chemistry

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AberrantDNAMethylation of Tumor Suppressor Genes and Oncogenes as Cancer Biomarkers

Alshammari¹,

Zhang²,

Sobota³

et al. 2022

Genomic and Epigenomic Biomarkers of Toxicology and Disease

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The cancer‐testis antigen BORIS phenocopies the tumor suppressor CTCF in normal and neoplastic cells

Tiffen

Bailey

Marshall

et al. 2013

Intl Journal of Cancer

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BORIS and CTCF are paralogous, multivalent 11-zinc finger transcription factors that play important roles in organizing higherorder chromatin architecture. BORIS is a cancer-testis antigen with a poorly defined function in cancer, although it has been hypothesized to exhibit oncogenic properties. CTCF, however, has been postulated as a candidate tumor suppressor. We collated the genetic lesions in BORIS and CTCF from multiple cancers identified using high-throughput genomics. In BORIS, nonsense and missense mutations are evenly distributed. In CTCF, recurrent mutations are mostly clustered in the conserved zinc finger domain and at residues critical for contacting DNA and zinc ion co-ordination. Three missense mutations are common to both proteins. We used an inducible lentivector to express wildtype BORIS or CTCF in primary cells and cancer cell lines in order to define their functional differences. Both BORIS and CTCF caused a significant decrease in cell proliferation and clonogenic capacity, without alteration of specific cell cycle phases. Both BORIS and CTCF conferred protective effects in primary cells and some cancer cells during UV damage-induced apoptosis. Using a bioluminescent MCF-7 orthotopic breast cancer model in vivo, we demonstrated that CTCF and BORIS suppressed breast cancer growth. These findings provide further evidence that CTCF behaves as a tumor suppressor, and show BORIS has a similar growth inhibitory effect in vitro and in vivo. Hence, acquired zinc finger mutations may disrupt these functions, thereby contributing to tumor growth and development.

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Expression of a Testis-Specific Form of Gal3st1 (CST), a Gene Essential for Spermatogenesis, Is Regulated by the CTCF Paralogous Gene BORIS

Cited by 72 publications

References 59 publications

Transcription Factor BORIS (Brother of the Regulator of Imprinted Sites) Directly Induces Expression of a Cancer-Testis Antigen, TSP50, through Regulated Binding of BORIS to the Promoter

Transcription Factor BORIS (Brother of the Regulator of Imprinted Sites) Directly Induces Expression of a Cancer-Testis Antigen, TSP50, through Regulated Binding of BORIS to the Promoter

AberrantDNAMethylation of Tumor Suppressor Genes and Oncogenes as Cancer Biomarkers

The cancer‐testis antigen BORIS phenocopies the tumor suppressor CTCF in normal and neoplastic cells

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