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YY1 control of mitochondrial-related genes does not account for regulation of immunoglobulin class switch recombination in mice.
European Journal of Immunology ( IF 4.5 ) Pub Date : 2020-02-24 , DOI: 10.1002/eji.201948385
Satabdi Nandi 1 , Guanxiang Liang 1 , Vishal Sindhava 1 , Rajesh Angireddy 1 , Arindam Basu 1 , Sarmistha Banerjee 1 , Suchita Hodawadekar 1 , Yue Zhang 1 , Narayan G Avadhani 1 , Ranjan Sen 2 , Michael L Atchison 1
Affiliation  

Immunoglobulin class switch recombination (CSR) occurs in activated B cells with increased mitochondrial mass and membrane potential. Transcription factor Yin Yang 1 (YY1) is critical for CSR and for formation of the DNA loops involved in this process. We therefore sought to determine if YY1 knockout impacts mitochondrial gene expression and mitochondrial function in murine splenic B cells, providing a potential mechanism for regulating CSR. We identified numerous genes in splenic B cells differentially regulated when cells are induced to undergo CSR. YY1 conditional knockout caused differential expression of 1129 genes, with 59 being mitochondrial‐related genes. ChIP‐seq analyses showed YY1 was directly bound to nearly half of these mitochondrial‐related genes. Surprisingly, at the time when YY1 knockout dramatically reduces DNA loop formation and CSR, mitochondrial mass and membrane potential were not significantly impacted, nor was there a significant change in mitochondrial oxygen consumption, extracellular acidification rate, or mitochondrial complex I or IV activities. Our results indicate that YY1 regulates numerous mitochondrial‐related genes in splenic B cells, but this does not account for the impact of YY1 on CSR or long‐distance DNA loop formation.

中文翻译:


YY1 对线粒体相关基因的控制不能解释小鼠中免疫球蛋白类别转换重组的调节。



免疫球蛋白类别转换重组 (CSR) 发生在线粒体质量和膜电位增加的活化 B 细胞中。转录因子 Yin Yang 1 (YY1) 对于 CSR 以及该过程中涉及的 DNA 环的形成至关重要。因此,我们试图确定 YY1 敲除是否会影响小鼠脾 B 细胞中的线粒体基因表达和线粒体功能,从而提供调节 CSR 的潜在机制。我们发现,当细胞被诱导进行 CSR 时,脾 B 细胞中的许多基因受到差异性调节。 YY1条件敲除导致1129个基因差异表达,其中59个是线粒体相关基因。 ChIP-seq 分析显示 YY1 直接与近一半的线粒体相关基因结合。令人惊讶的是,当YY1敲除显着减少DNA环形成和CSR时,线粒体质量和膜电位没有受到显着影响,线粒体耗氧量、细胞外酸化率或线粒体复合物I或IV活性也没有显着变化。我们的结果表明,YY1 调节脾 B 细胞中的许多线粒体相关基因,但这并不能解释 YY1 对 CSR 或长距离 DNA 环形成的影响。
更新日期:2020-02-24
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