Kdm2b maintains murine embryonic stem cell status by recruiting PRC1 complex to CpG islands of lineage genes [Expression profiling]

Polycomb group (PcG) proteins play important roles in repressing lineage-specific genes and maintaining the undifferentiated state of mouse embryonic stem cells (mESCs). However, the mechanisms by which PcG proteins are recruited to their targets are largely unknown. Here, we show that the histone demethylase Kdm2b is highly expressed in mESCs and regulated by the pluripotent factors Oct4/Sox2 directly. Depletion of Kdm2b in mESCs causes de-repression of lineage-specific genes and induces early differentiation. The function of Kdm2b depends on its CXXC-ZF domain, which mediates Kdm2b’s genome-wide binding to CpG islands (CGIs). Kdm2b interacts with the core components of the Polycomb repressive complex 1 (PRC1) and recruits the complex to the CGIs of early lineage-specific genes. Thus, our study not only reveals a novel Oct4/Sox2-Kdm2b-PRC1-CGI regulatory axis and its function in maintaining undifferentiated state of mESCs, but also demonstrates a critical function of Kdm2b in recruiting PRC1 to the CGIs of lineage-specific genes to repress their expression. In this dataset, we include the expression data for control and Kdm2b knockdown mouse embryonic stem cells. We analyzed the gene expression in control and Kdm2b knockdown mouse embryonic stem cells using the Affymetrix MoGene-1_0-st-v1 platform.

多梳蛋白家族（Polycomb group, PcG）在抑制谱系特异性基因表达、维持小鼠胚胎干细胞（mouse embryonic stem cells, mESCs）未分化状态中发挥重要作用。然而，PcG蛋白被招募至靶位点的分子机制在很大程度上仍未明确。本研究证实，组蛋白去甲基化酶Kdm2b在mESCs中呈高表达状态，且直接受多能性因子Oct4/Sox2调控。在mESCs中敲降Kdm2b会导致谱系特异性基因去抑制，并诱导细胞发生早期分化。Kdm2b的功能依赖于其CXXC型锌指结构域（CXXC-ZF domain），该结构域可介导Kdm2b在全基因组范围内结合CpG岛（CpG islands, CGIs）。Kdm2b可与多梳抑制复合体1（Polycomb repressive complex 1, PRC1）的核心组分相互作用，并将该复合体招募至早期谱系特异性基因的CpG岛区域。综上，本研究不仅揭示了一条全新的Oct4/Sox2-Kdm2b-PRC1-CGI调控轴及其在维持mESCs未分化状态中的功能，同时证实了Kdm2b在招募PRC1至谱系特异性基因CpG岛以抑制其表达过程中的关键作用。本数据集包含对照组与Kdm2b敲降组小鼠胚胎干细胞的基因表达数据，我们采用Affymetrix MoGene-1_0-st-v1芯片平台对两组细胞的基因表达水平进行了分析。