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Basic leucine zipper transcription factor, ATF-like (BATF) regulates epigenetically and energetically effector CD8 T-cell differentiation via Sirt1 expression.

ABSTRACT: CD8 T cells play a critical role in protection against viral infections. During effector differentiation, CD8 T cells dramatically change chromatin structure and cellular metabolism, but how energy production increases in response to these epigenetic changes is unknown. We found that loss of basic leucine zipper transcription factor, ATF-like (BATF) inhibited effector CD8 T-cell differentiation. At the late effector stage, BATF was induced by IL-12 and required for IL-12-mediated histone acetylation and survival of effector T cells. BATF, together with c-Jun, transcriptionally inhibited expression of the nicotinamide adenine dinucleotide (NAD(+))-dependent deacetylase Sirt1, resulting in increased histone acetylation of the T-bet locus and increased cellular NAD(+), which increased ATP production. In turn, high levels of T-bet expression and ATP production promoted effector differentiation and cell survival. These results suggest that BATF promotes effector CD8 T-cell differentiation by regulating both epigenetic remodeling and energy metabolism through Sirt1 expression.

SUBMITTER: Kuroda S

PROVIDER: S-EPMC3169148 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

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Basic leucine zipper transcription factor, ATF-like (BATF) regulates epigenetically and energetically effector CD8 T-cell differentiation via Sirt1 expression.

Kuroda Shoko S Yamazaki Maya M Abe Manabu M Sakimura Kenji K Takayanagi Hiroshi H Iwai Yoshiko Y

Proceedings of the National Academy of Sciences of the United States of America 20110822 36

CD8 T cells play a critical role in protection against viral infections. During effector differentiation, CD8 T cells dramatically change chromatin structure and cellular metabolism, but how energy production increases in response to these epigenetic changes is unknown. We found that loss of basic leucine zipper transcription factor, ATF-like (BATF) inhibited effector CD8 T-cell differentiation. At the late effector stage, BATF was induced by IL-12 and required for IL-12-mediated histone acetyla ...[more]

PMID: 21873234

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Project description:BackgroundBasic leucine zipper ATF-like transcription factor 2 (BATF2) has been reported to participate in the occurrence and development of some malignancies. Herein, we aimed to explore the expression pattern and clinical implications of BATF2 in breast cancer (BC).MethodsWe assessed the differences in BATF2 mRNA expression between cancerous and noncancerous tissues in BC using GEPIA and UALCAN data and in BATF2 protein expression pattern using Human Protein Atlas (HPA) data. BATF2 co-expression networks were analyzed in Coexpedia. The association between the differentially expressed BATF2 mRNA and BC prognosis was assessed using UALCAN, OSbrca, and GEPIA databases. In external validations, BATF2 protein expression in BC tissues was quantitated using a tissue microarray and immunohistochemistry (IHC) analysis, and BATF2 mRNA expression in serum and serum-derived exosomes of BC patients using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR).ResultsNo difference in the BATF2 mRNA expression level was found between cancerous and noncancerous tissues in BC based on databases. There were low-to-moderate levels of increases in BATF2 protein expressions in BC cases from the HPA cohort. BATF2 mRNA expression was negatively correlated with androgen receptor (AR) and positively correlated with BRCA2 DNA repair associated (BRCA2), marker of proliferation Ki-67 (Mki67), and tumor protein p53 (TP53) expressions. Generally, BATF2 mRNA exhibited a non-significant association with BC prognosis; yet the subgroup analyses showed that triple-negative breast cancer (TNBC) patients with high BATF2 mRNA expressions had a longer overall survival (OS). Our IHC analysis revealed a positive rate of BATF2 protein expression of 46.90%, mainly located in the nucleus of cancer cells in BC, and the OS of BC patients with high BATF2 protein expressions was prolonged. The positive rates of BATF2 mRNA expressions in the serum and exosomes were 45.00 and 41.67%, respectively. Besides, the AUCs of serum and exosomal BATF2 mRNA for BC diagnosis were 0.8929 and 0.8869, respectively.ConclusionsBC patients exhibit low-to-moderate expressions in BATF2 mRNA expression levels in cancerous tissues. The high BATF2 protein expression can be a potential indicator of a better BC prognosis. Serum and exosomal BATF2 mRNA levels also serve as promising noninvasive biomarkers for BC diagnosis.

Dataset Information

Basic leucine zipper transcription factor, ATF-like (BATF) regulates epigenetically and energetically effector CD8 T-cell differentiation via Sirt1 expression.

Publications

Basic leucine zipper transcription factor, ATF-like (BATF) regulates epigenetically and energetically effector CD8 T-cell differentiation via Sirt1 expression.

Similar Datasets

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