YY1 control of mitochondrial‐related genes does not account for regulation of immunoglobulin class switch recombination in mice

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. Knock‐out of transcription factor YY1 dramatically reduces immunoglobulin class switch recombination (CSR), but this reduction occurs prior to drops in mitochondrial metabolic functions and cell viability. Therefore, the CSR after YY1 knock‐out is not due to these functions, but may be due to YY1 impact on DNA interactions needed for CSR.