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

YY1在早期和晚期B细胞分化中调控的基因和通路

• 批准号: 8974267
• 负责人: ANN J FEENEY
• 金额: $ 9.48万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-12-01 至 2016-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8974267
• 关键词: Antibody Affinity; Area; B cell differentiation; B-Lymphocyte Subsets; B-Lymphocytes; Binding; Binding Sites; Bone Marrow; C57BL/6 Mouse; CD19 gene; ChIP-seq; Coupled; Data; Enhancers; Future; Gene Expression Microarray Analysis; Genes; Health; Histones; Immunization; Immunoglobulin Class Switching; Immunoglobulin Somatic Hypermutation; Immunoglobulin Switch Recombination; LoxP-flanked allele; Lymphocyte; Mus; Paper; Pathway interactions; Pattern; Peripheral; Plasma Cells; Post-Translational Protein Processing; Publishing; Regulation; Rest; Role; Site; Sorting - Cell Movement; Spleen; Staging; Structure of germinal center of lymph node; Testing; Vaccines; Yin-Yang; base; cell type; genetic signature; in vivo; insight; pathogen; promoter; transcription factor; transcriptome sequencing

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.

描述（由申请人提供）：YY 1（阴阳1号）是一种普遍表达的转录因子，具有抑制和激活活性。它在骨髓和脾脏中的11个B细胞亚群中高度表达，但除了它在早期前B细胞分化中的重要作用外，关于YY 1在B细胞分化中的作用知之甚少。然而，最近发表了一项研究，其中通过对B细胞亚群的微阵列数据的基因表达分析确定的对B细胞分化的每个阶段特异的基因，被生物信息学地分析了转录因子结合位点。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YY 1基序。因此，他们得出结论，YY 1可能是GC分化的关键调节因子。为了验证这一假设，我们将YY 1 floxed小鼠与C β 1-cre小鼠杂交，结果在免疫后8天没有观察到GC B细胞或浆细胞。然而，由于YY 1在所有B细胞亚群中表达，我们还将floxed YY 1小鼠与CD 19-Cre小鼠杂交，以确定YY 1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YY 1。因此，我们希望分析我们已经存在的或即将获得的ChIP-seq和RNA-seq数据，以全面了解这种重要的转录因子调节哪些基因和途径，这些基因和途径中有多少是所有B细胞亚群共有的，以及YY 1的调节活性在某些分化阶段（例如GC B细胞或早期B细胞分化）中有多少是独特的。此外，对YY 1结合位点附近富集的其他转录因子的基序的分析可以提供对在B细胞分化的特定阶段调节分化和功能的潜在转录网络的洞察。