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56 reviewsSUMMARYGene expression is orchestrated by transcription factors, which function within the context of a three-dimensional genome. Zinc-finger protein 143 (ZNF143/ZFP143) is a transcription factor that has been implicated inboth gene activation and chromatin looping. To study the direct consequences of ZNF143/ZFP143 loss, wegenerated a ZNF143/ZFP143 depletion system in mouse embryonic stem cells. Our results show thatZNF143/ZFP143 degradation has no effect on chromatin looping. Systematic analysis of ZNF143/ZFP143occupancy data revealed that a commonly used antibody cross-reacts with CTCF, leading to its incorrect association with chromatin loops. Nevertheless, ZNF143/ZFP143 specifically activates nuclear-encoded mitochondrial genes, and its loss leads to severe mitochondrial dysfunction. Using an in vitro embryo model, wefind that ZNF143/ZFP143 is an essential regulator of organismal development. Our results establish ZNF143/ZFP143 as a conserved transcriptional regulator of cell proliferation and differentiation by safeguarding mitochondrial activity.
