Genes and pathways regulated by YY1 in early and late B cell differentiation

描述（由申请人提供）：YY1 （Yin-yang 1）是一种普遍表达的转录因子，具有抑制和激活活性。它在骨髓和脾脏的所有B细胞亚群中都高度表达，但除了在早期前B细胞分化中发挥重要作用外，对YY1在B细胞分化中的作用知之甚少。然而，最近发表的一项研究中，通过对B细胞亚群微阵列数据的基因表达分析确定了B细胞分化各个阶段的特异性基因，并对转录因子结合位点进行了生物信息学分析。他们发现生发中心B细胞（GC）的特征基因，而不是其他B细胞分化亚群的特征基因，富集了YY1基序。因此，他们得出结论，YY1可能是GC分化的关键调节因子。为了验证这一假设，我们将YY1粘接小鼠与c1 -cre小鼠杂交，免疫后8天确实没有观察到GC B细胞和浆细胞。然而，由于YY1在所有B细胞亚群中都有表达，我们也将带floxed的YY1小鼠与CD19-Cre小鼠杂交，以确定YY1在其他亚群中是否重要，我们发现所有外周B细胞亚群都需要YY1。因此，我们希望分析已经存在或即将获得的ChIP-seq和RNA-seq数据，以全面了解这种重要转录因子调控的基因和途径，这些基因和途径中有多少是所有B细胞亚群共同的，YY1的调控活性有多少是特定分化阶段（例如GC B细胞或早期B细胞分化）所特有的。此外，对YY1结合位点附近富集的其他转录因子的基序的分析可能有助于深入了解在B细胞分化的特定阶段调节分化和功能的潜在转录网络。

DESCRIPTION (provided by applicant): 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.