假定的成环因子ZNF143/ZFP143是一种没有成环功能的必需转录调节因子。
Putative looping factor ZNF143/ZFP143 is an essential transcriptional regulator with no looping function.
作者信息
Narducci Domenic N, Hansen Anders S
机构信息
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; The Novo Nordisk Foundation Center for Genomic Mechanisms of Disease, Gene Regulation Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA; Koch Institute for Integrative Cancer Research, Cambridge, MA 02139, USA.
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; The Novo Nordisk Foundation Center for Genomic Mechanisms of Disease, Gene Regulation Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA; Koch Institute for Integrative Cancer Research, Cambridge, MA 02139, USA.
出版信息
Mol Cell. 2025 Jan 2;85(1):9-23.e9. doi: 10.1016/j.molcel.2024.11.032. Epub 2024 Dec 20.
Interactions between distal loci, including those involving enhancers and promoters, are a central mechanism of gene regulation in mammals, yet the protein regulators of these interactions remain largely undetermined. The zinc-finger transcription factor (TF) ZNF143/ZFP143 has been strongly implicated as a regulator of chromatin interactions, functioning either with or without CTCF. However, how ZNF143/ZFP143 functions as a looping factor is not well understood. Here, we tagged both CTCF and ZNF143/ZFP143 with dual-purpose degron/imaging tags to combinatorially assess their looping function and effect on each other. We find that ZNF143/ZFP143, contrary to prior reports, possesses no general looping function in mouse and human cells and that it largely functions independently of CTCF. Instead, ZNF143/ZFP143 is an essential and highly conserved transcription factor that largely binds promoters proximally, exhibits an extremely stable chromatin dwell time (>20 min), and regulates an important subset of mitochondrial and ribosomal genes.
包括那些涉及增强子和启动子的远端基因座之间的相互作用，是哺乳动物基因调控的核心机制，然而这些相互作用的蛋白质调节因子在很大程度上仍未确定。锌指转录因子（TF）ZNF143/ZFP143已被强烈认为是染色质相互作用的调节因子，其作用依赖或不依赖于CTCF。然而，ZNF143/ZFP143作为一种成环因子是如何发挥作用的，目前还不太清楚。在这里，我们用两用降解子/成像标签标记了CTCF和ZNF143/ZFP143，以综合评估它们的成环功能以及彼此之间的影响。我们发现，与之前的报道相反，ZNF143/ZFP143在小鼠和人类细胞中不具有一般的成环功能，并且在很大程度上独立于CTCF发挥作用。相反，ZNF143/ZFP143是一种必不可少且高度保守的转录因子，它主要在启动子近端结合，具有极稳定的染色质驻留时间（>20分钟），并调节线粒体和核糖体基因的一个重要子集。
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