YY1 (Yin-yang 1) is a ubiquitously expressed transcription factor that has both repressive and activating activities. It is highly expressed in ll B cell subsets both in the bone marrow and spleen, yet very little is known about the roles of YY1 in B cell differentiation other than its essential role in early pro-B cell differentiation. However, a study was recently published in which the genes that were specific for each stage of B cell differentiation, as determined by gene expression analysis of microarray data on B cell subsets, were analyzed bioinformatically for transcription factor binding sites. They found that the germinal center B cell (GC) signature genes, but not the signature genes of other B cell differentiation subsets, were enriched for the YY1 motif. Thus, they concluded that YY1 may be a key regulator of GC differentiation. In order to test this hypothesis, we crossed YY1 floxed mice to C?1-cre mice, and indeed, no GC B cells or plasma cells were observed 8 days after immunization. However, since YY1 was expressed in all B cell subsets, we also crossed the floxed YY1 mice to CD19-Cre mice to determine if YY1 was important in other subsets, and we found that all peripheral B cell subsets need YY1. Hence we wish to analyze our already existing, or soon to be obtained, ChIP-seq and RNA-seq data to gain a complete understanding of what genes and pathways are regulated by this important transcription factor, how many of these genes and pathways are common for all B cell subsets, and how much of YY1's regulatory activity is unique for certain stages of differentiation, e.g. GC B cells, or early B cel differentiation. In addition, analyses of motifs for other transcription factors that are enriched near the YY1 binding sites may provide insight into potential transcriptional networks regulating differentiation and function at specific stages of B cell differentiation.
The transcription factor YY1 has been predicted to specifically regulate many genes in germinal center B cells, but this has not been experimentally tested. The regulation of the differentiation of germinal center B cells is critical to understand since these are the lymphocytes that respond to vaccines by undergoing somatic hypermutation and class switch recombination to produce high affinity antibodies that can be protective against a variety of pathogens.
| Kleiman, Eden; Jia, Haiqun; Loguercio, Salvatore et al. (2016) YY1 plays an essential role at all stages of B-cell differentiation. Proc Natl Acad Sci U S A 113:E3911-20 |
