Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom.
Mol Cell Biol. 2013 Oct;33(19):3936-50. doi: 10.1128/MCB.00498-13. Epub 2013 Aug 5.
Prdm4 is a highly conserved member of the Prdm family of PR/SET domain zinc finger proteins. Many well-studied Prdm family members play critical roles in development and display striking loss-of-function phenotypes. Prdm4 functional contributions have yet to be characterized. Here, we describe its widespread expression in the early embryo and adult tissues. We demonstrate that DNA binding is exclusively mediated by the Prdm4 zinc finger domain, and we characterize its tripartite consensus sequence via SELEX (systematic evolution of ligands by exponential enrichment) and ChIP-seq (chromatin immunoprecipitation-sequencing) experiments. In embryonic stem cells (ESCs), Prdm4 regulates key pluripotency and differentiation pathways. Two independent strategies, namely, targeted deletion of the zinc finger domain and generation of a EUCOMM LacZ reporter allele, resulted in functional null alleles. However, homozygous mutant embryos develop normally and adults are healthy and fertile. Collectively, these results strongly suggest that Prdm4 functions redundantly with other transcriptional partners to cooperatively regulate gene expression in the embryo and adult animal.
PRDM4 是 PR/SET 结构域锌指蛋白 PRDM 家族中的高度保守成员。许多研究充分的 PRDM 家族成员在发育中发挥关键作用，并表现出显著的功能丧失表型。PRDM4 的功能贡献尚未得到表征。在这里，我们描述了它在早期胚胎和成年组织中的广泛表达。我们证明 DNA 结合仅由 Prdm4 锌指结构域介导，并且我们通过 SELEX（通过指数富集的配体系统进化）和 ChIP-seq（染色质免疫沉淀测序）实验对其三分体保守序列进行了表征。在胚胎干细胞（ESCs）中，PRDM4 调节关键的多能性和分化途径。两种独立的策略，即锌指结构域的靶向缺失和 EUCOMM LacZ 报告基因等位基因的产生，导致了功能缺失等位基因。然而，纯合突变体胚胎正常发育，成年个体健康且有生育能力。总的来说，这些结果强烈表明，PRDM4 与其他转录伙伴一起发挥冗余功能，以协同调控胚胎和成年动物的基因表达。
