High-resolution chromatin immunoprecipitation (ChIP) sequencing reveals novel binding targets and prognostic role for SOX11 in mantle cell lymphoma

P. Y. Kuo, W. Leshchenko, M. J. Fazzari, D. Perumal, T. Gellen, T. He, J. Iqbal, S. Baumgartner-Wennerholm, L. Nygren, F. Zhang, W. Zhang, K. S. Suh, A. Goy, D. T. Yang, W. C. Chan, B. S. Kahl, Amit K. Verma, R. D. Gascoyne, E. Kimby, B. Sander & 3 others B. Hilda Ye, A. M. Melnick, S. Parekh

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Abstract

Sex determining region Y-box 11 (SOX11) expression is specific for mantle cell lymphoma (MCL) as compared with other non-Hodgkin's lymphomas. However, the function and direct-binding targets of SOX11 in MCL are largely unknown. We used high-resolution chromatin immunoprecipitation sequencing to identify the direct target genes of SOX11 in a genome-wide, unbiased manner and elucidate its functional significance. Pathway analysis identified WNT, PKA and TGF-beta signaling pathways as significantly enriched by SOX11-target genes. Quantitative chromatin immunoprecipitation sequencing and promoter reporter assays confirmed that SOX11 directly binds to individual genes and modulates their transcription activities in these pathways in MCL. Functional studies using RNA interference demonstrate that SOX11 directly regulates WNT in MCL. We analyzed SOX11 expression in three independent well-annotated tissue microarrays from the University of Wisconsin (UW), Karolinska Institute and British Columbia Cancer Agency. Our findings suggest that high SOX11 expression is associated with improved survival in a subset of MCL patients, particularly those treated with intensive chemotherapy. Transcriptional regulation of WNT and other biological pathways affected by SOX11-target genes may help explain the impact of SOX11 expression on patient outcomes.

Original languageEnglish (US)
Pages (from-to)1231-1240
Number of pages10
JournalOncogene
Volume34
Issue number10
DOIs
StatePublished - Mar 5 2015

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Mantle-Cell Lymphoma
Chromatin Immunoprecipitation
Genes
British Columbia
RNA Interference
Transforming Growth Factor beta
Non-Hodgkin's Lymphoma
Genome
Drug Therapy
Survival
Neoplasms

ASJC Scopus subject areas

  • Medicine(all)

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High-resolution chromatin immunoprecipitation (ChIP) sequencing reveals novel binding targets and prognostic role for SOX11 in mantle cell lymphoma. / Kuo, P. Y.; Leshchenko, W.; Fazzari, M. J.; Perumal, D.; Gellen, T.; He, T.; Iqbal, J.; Baumgartner-Wennerholm, S.; Nygren, L.; Zhang, F.; Zhang, W.; Suh, K. S.; Goy, A.; Yang, D. T.; Chan, W. C.; Kahl, B. S.; Verma, Amit K.; Gascoyne, R. D.; Kimby, E.; Sander, B.; Ye, B. Hilda; Melnick, A. M.; Parekh, S.

In: Oncogene, Vol. 34, No. 10, 05.03.2015, p. 1231-1240.

Research output: Contribution to journalArticle

Kuo, PY, Leshchenko, W, Fazzari, MJ, Perumal, D, Gellen, T, He, T, Iqbal, J, Baumgartner-Wennerholm, S, Nygren, L, Zhang, F, Zhang, W, Suh, KS, Goy, A, Yang, DT, Chan, WC, Kahl, BS, Verma, AK, Gascoyne, RD, Kimby, E, Sander, B, Ye, BH, Melnick, AM & Parekh, S 2015, 'High-resolution chromatin immunoprecipitation (ChIP) sequencing reveals novel binding targets and prognostic role for SOX11 in mantle cell lymphoma', Oncogene, vol. 34, no. 10, pp. 1231-1240. https://doi.org/10.1038/onc.2014.44
Kuo, P. Y. ; Leshchenko, W. ; Fazzari, M. J. ; Perumal, D. ; Gellen, T. ; He, T. ; Iqbal, J. ; Baumgartner-Wennerholm, S. ; Nygren, L. ; Zhang, F. ; Zhang, W. ; Suh, K. S. ; Goy, A. ; Yang, D. T. ; Chan, W. C. ; Kahl, B. S. ; Verma, Amit K. ; Gascoyne, R. D. ; Kimby, E. ; Sander, B. ; Ye, B. Hilda ; Melnick, A. M. ; Parekh, S. / High-resolution chromatin immunoprecipitation (ChIP) sequencing reveals novel binding targets and prognostic role for SOX11 in mantle cell lymphoma. In: Oncogene. 2015 ; Vol. 34, No. 10. pp. 1231-1240.
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abstract = "Sex determining region Y-box 11 (SOX11) expression is specific for mantle cell lymphoma (MCL) as compared with other non-Hodgkin's lymphomas. However, the function and direct-binding targets of SOX11 in MCL are largely unknown. We used high-resolution chromatin immunoprecipitation sequencing to identify the direct target genes of SOX11 in a genome-wide, unbiased manner and elucidate its functional significance. Pathway analysis identified WNT, PKA and TGF-beta signaling pathways as significantly enriched by SOX11-target genes. Quantitative chromatin immunoprecipitation sequencing and promoter reporter assays confirmed that SOX11 directly binds to individual genes and modulates their transcription activities in these pathways in MCL. Functional studies using RNA interference demonstrate that SOX11 directly regulates WNT in MCL. We analyzed SOX11 expression in three independent well-annotated tissue microarrays from the University of Wisconsin (UW), Karolinska Institute and British Columbia Cancer Agency. Our findings suggest that high SOX11 expression is associated with improved survival in a subset of MCL patients, particularly those treated with intensive chemotherapy. Transcriptional regulation of WNT and other biological pathways affected by SOX11-target genes may help explain the impact of SOX11 expression on patient outcomes.",
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AU - Kuo, P. Y.

AU - Leshchenko, W.

AU - Fazzari, M. J.

AU - Perumal, D.

AU - Gellen, T.

AU - He, T.

AU - Iqbal, J.

AU - Baumgartner-Wennerholm, S.

AU - Nygren, L.

AU - Zhang, F.

AU - Zhang, W.

AU - Suh, K. S.

AU - Goy, A.

AU - Yang, D. T.

AU - Chan, W. C.

AU - Kahl, B. S.

AU - Verma, Amit K.

AU - Gascoyne, R. D.

AU - Kimby, E.

AU - Sander, B.

AU - Ye, B. Hilda

AU - Melnick, A. M.

AU - Parekh, S.

PY - 2015/3/5

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N2 - Sex determining region Y-box 11 (SOX11) expression is specific for mantle cell lymphoma (MCL) as compared with other non-Hodgkin's lymphomas. However, the function and direct-binding targets of SOX11 in MCL are largely unknown. We used high-resolution chromatin immunoprecipitation sequencing to identify the direct target genes of SOX11 in a genome-wide, unbiased manner and elucidate its functional significance. Pathway analysis identified WNT, PKA and TGF-beta signaling pathways as significantly enriched by SOX11-target genes. Quantitative chromatin immunoprecipitation sequencing and promoter reporter assays confirmed that SOX11 directly binds to individual genes and modulates their transcription activities in these pathways in MCL. Functional studies using RNA interference demonstrate that SOX11 directly regulates WNT in MCL. We analyzed SOX11 expression in three independent well-annotated tissue microarrays from the University of Wisconsin (UW), Karolinska Institute and British Columbia Cancer Agency. Our findings suggest that high SOX11 expression is associated with improved survival in a subset of MCL patients, particularly those treated with intensive chemotherapy. Transcriptional regulation of WNT and other biological pathways affected by SOX11-target genes may help explain the impact of SOX11 expression on patient outcomes.

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