MAGEA1 inhibits the expression of BORIS via increased promoter methylation

Jizhong Zhao, Yueqing Wang, Qianjin Liang, Yan Xu, Jianli Sang

Research output: Contribution to journalArticle

Abstract

Melanoma-associated antigen A1 (MAGEA1) and BORIS (also known as CTCFL) are members of the cancer testis antigen (CTA) family. Their functions and expression-regulation mechanisms are not fully understood. In this study, we reveal new functions and regulatory mechanisms of MAGEA1 and BORIS in breast cancer cells, which we investigated in parental and genetically manipulated breast cancer cells via gene overexpression or siRNA-mediated downregulation. We identified the interaction between MAGEA1 and CTCF, which is required for the binding of MAGEA1 to the BORIS promoter and is critical for the recruitment of DNMT3a. A protein complex containing MAGEA1, CTCF and DNMT3a was formed before or after conjunction with the BORIS promoter. The binding of this complex to the BORIS promoter accounts for the hypermethylation and repression of BORIS expression, which results in cell death in the breast cancer cell lines tested. Multiple approaches were employed, including co-immunoprecipitation, glutathione S-transferase pull-down assay, co-localization and cell death analyses using annexin V-FITC/ propidium iodide double-staining and caspase 3 activation assays, chromatin immunoprecipitation and bisulfite sequencing PCR assays for methylation. Our results have implications for the development of strategies in CTA-based immune therapeutics.

Original languageEnglish (US)
Article numberjcs218628
JournalJournal of Cell Science
Volume132
Issue number1
DOIs
StatePublished - Jan 1 2019

Fingerprint

Melanoma-Specific Antigens
Methylation
Testicular Neoplasms
Breast Neoplasms
Cell Death
Antigens
Propidium
Fluorescein-5-isothiocyanate
Chromatin Immunoprecipitation
Annexin A5
Glutathione Transferase
Immunoprecipitation
Caspase 3
Small Interfering RNA
Down-Regulation
Staining and Labeling
Cell Line
Polymerase Chain Reaction
Genes
Proteins

Keywords

  • Apoptosis
  • BORIS
  • CTCF
  • MAGEA1
  • Methylation

ASJC Scopus subject areas

  • Cell Biology

Cite this

MAGEA1 inhibits the expression of BORIS via increased promoter methylation. / Zhao, Jizhong; Wang, Yueqing; Liang, Qianjin; Xu, Yan; Sang, Jianli.

In: Journal of Cell Science, Vol. 132, No. 1, jcs218628, 01.01.2019.

Research output: Contribution to journalArticle

Zhao, Jizhong ; Wang, Yueqing ; Liang, Qianjin ; Xu, Yan ; Sang, Jianli. / MAGEA1 inhibits the expression of BORIS via increased promoter methylation. In: Journal of Cell Science. 2019 ; Vol. 132, No. 1.
@article{5e564c7e6c4e40eda520ce413caa3a8c,
title = "MAGEA1 inhibits the expression of BORIS via increased promoter methylation",
abstract = "Melanoma-associated antigen A1 (MAGEA1) and BORIS (also known as CTCFL) are members of the cancer testis antigen (CTA) family. Their functions and expression-regulation mechanisms are not fully understood. In this study, we reveal new functions and regulatory mechanisms of MAGEA1 and BORIS in breast cancer cells, which we investigated in parental and genetically manipulated breast cancer cells via gene overexpression or siRNA-mediated downregulation. We identified the interaction between MAGEA1 and CTCF, which is required for the binding of MAGEA1 to the BORIS promoter and is critical for the recruitment of DNMT3a. A protein complex containing MAGEA1, CTCF and DNMT3a was formed before or after conjunction with the BORIS promoter. The binding of this complex to the BORIS promoter accounts for the hypermethylation and repression of BORIS expression, which results in cell death in the breast cancer cell lines tested. Multiple approaches were employed, including co-immunoprecipitation, glutathione S-transferase pull-down assay, co-localization and cell death analyses using annexin V-FITC/ propidium iodide double-staining and caspase 3 activation assays, chromatin immunoprecipitation and bisulfite sequencing PCR assays for methylation. Our results have implications for the development of strategies in CTA-based immune therapeutics.",
keywords = "Apoptosis, BORIS, CTCF, MAGEA1, Methylation",
author = "Jizhong Zhao and Yueqing Wang and Qianjin Liang and Yan Xu and Jianli Sang",
year = "2019",
month = "1",
day = "1",
doi = "10.1242/jcs.218628",
language = "English (US)",
volume = "132",
journal = "Journal of Cell Science",
issn = "0021-9533",
publisher = "Company of Biologists Ltd",
number = "1",

}

TY - JOUR

T1 - MAGEA1 inhibits the expression of BORIS via increased promoter methylation

AU - Zhao, Jizhong

AU - Wang, Yueqing

AU - Liang, Qianjin

AU - Xu, Yan

AU - Sang, Jianli

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Melanoma-associated antigen A1 (MAGEA1) and BORIS (also known as CTCFL) are members of the cancer testis antigen (CTA) family. Their functions and expression-regulation mechanisms are not fully understood. In this study, we reveal new functions and regulatory mechanisms of MAGEA1 and BORIS in breast cancer cells, which we investigated in parental and genetically manipulated breast cancer cells via gene overexpression or siRNA-mediated downregulation. We identified the interaction between MAGEA1 and CTCF, which is required for the binding of MAGEA1 to the BORIS promoter and is critical for the recruitment of DNMT3a. A protein complex containing MAGEA1, CTCF and DNMT3a was formed before or after conjunction with the BORIS promoter. The binding of this complex to the BORIS promoter accounts for the hypermethylation and repression of BORIS expression, which results in cell death in the breast cancer cell lines tested. Multiple approaches were employed, including co-immunoprecipitation, glutathione S-transferase pull-down assay, co-localization and cell death analyses using annexin V-FITC/ propidium iodide double-staining and caspase 3 activation assays, chromatin immunoprecipitation and bisulfite sequencing PCR assays for methylation. Our results have implications for the development of strategies in CTA-based immune therapeutics.

AB - Melanoma-associated antigen A1 (MAGEA1) and BORIS (also known as CTCFL) are members of the cancer testis antigen (CTA) family. Their functions and expression-regulation mechanisms are not fully understood. In this study, we reveal new functions and regulatory mechanisms of MAGEA1 and BORIS in breast cancer cells, which we investigated in parental and genetically manipulated breast cancer cells via gene overexpression or siRNA-mediated downregulation. We identified the interaction between MAGEA1 and CTCF, which is required for the binding of MAGEA1 to the BORIS promoter and is critical for the recruitment of DNMT3a. A protein complex containing MAGEA1, CTCF and DNMT3a was formed before or after conjunction with the BORIS promoter. The binding of this complex to the BORIS promoter accounts for the hypermethylation and repression of BORIS expression, which results in cell death in the breast cancer cell lines tested. Multiple approaches were employed, including co-immunoprecipitation, glutathione S-transferase pull-down assay, co-localization and cell death analyses using annexin V-FITC/ propidium iodide double-staining and caspase 3 activation assays, chromatin immunoprecipitation and bisulfite sequencing PCR assays for methylation. Our results have implications for the development of strategies in CTA-based immune therapeutics.

KW - Apoptosis

KW - BORIS

KW - CTCF

KW - MAGEA1

KW - Methylation

UR - http://www.scopus.com/inward/record.url?scp=85059501367&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85059501367&partnerID=8YFLogxK

U2 - 10.1242/jcs.218628

DO - 10.1242/jcs.218628

M3 - Article

C2 - 30498011

AN - SCOPUS:85059501367

VL - 132

JO - Journal of Cell Science

JF - Journal of Cell Science

SN - 0021-9533

IS - 1

M1 - jcs218628

ER -