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Putative looping factor ZNF143/ZFP143 is an essential transcriptional regulator with no looping function [PRO-seq]

ABSTRACT: Interactions between distal loci in mammalian genomes, including those involving enhancers and promoters, are thought to be a central mechanism of gene regulation in mammals, yet the protein regulators of these interactions remain largely undetermined. The zinc finger transcription factor ZNF143/ZFP143 has been strongly implicated as a factor that regulates chromatin interactions, functioning either with or without CTCF. However, ZNF143/ZFP143’s role in this process and its function with or without CTCF are not well understood. Here, we tagged both CTCF and ZNF143/ZFP143 with dual-purpose degron/imaging tags to combinatorically assess their loop function and effect on each other. We find that ZNF143/ZFP143 possesses no general looping function, and that it largely functions independently to CTCF. Instead, ZNF143/ZFP143 is an essential and highly conserved transcription factor possessing an extremely stable chromatin residence time (>20 min) that regulates an important subset of mitochondrial and ribosomal genes.

ORGANISM(S): Mus musculus

PROVIDER: GSE256227 | GEO | 2024/03/07

REPOSITORIES: GEO

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Putative looping factor ZNF143/ZFP143 is an essential transcriptional regulator with no looping function [ChIP-seq]

Project description:Interactions between distal loci in mammalian genomes, including those involving enhancers and promoters, are thought to be a central mechanism of gene regulation in mammals, yet the protein regulators of these interactions remain largely undetermined. The zinc finger transcription factor ZNF143/ZFP143 has been strongly implicated as a factor that regulates chromatin interactions, functioning either with or without CTCF. However, ZNF143/ZFP143’s role in this process and its function with or without CTCF are not well understood. Here, we tagged both CTCF and ZNF143/ZFP143 with dual-purpose degron/imaging tags to combinatorically assess their loop function and effect on each other. We find that ZNF143/ZFP143 possesses no general looping function, and that it largely functions independently to CTCF. Instead, ZNF143/ZFP143 is an essential and highly conserved transcription factor possessing an extremely stable chromatin residence time (>20 min) that regulates an important subset of mitochondrial and ribosomal genes.

2024-03-07 | GSE256226 | GEO

Putative looping factor ZNF143/ZFP143 is an essential transcriptional regulator with no looping function [Micro-C]

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ZNF143 is a transcriptional regulator of nuclear-encoded mitochondrial genes that acts independently of looping and CTCF

Project description:Gene 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 in both gene activation and chromatin looping. To study the direct consequences of ZNF143/ZFP143 loss, we generated a ZNF143/ZFP143 degron line. Our results show that ZNF143/ZFP143 depletion has no effect on chromatin looping. Systematic analysis of ZNF143/ZFP143 occupancy 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, we find 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.

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ZNF143 is a transcriptional regulator of nuclear-encoded mitochondrial genes that acts independently of looping and CTCF

Project description:Gene expression is orchestrated by transcription factors (TFs), which bind to DNA in a sequence-specific manner, and by spatial genome structure, which constrains and shapes TF activity. Zinc finger protein 143 (ZNF143/ZFP143) is a TF that has been implicated in both gene activation and 3D genome organisation. We have generated an acute ZNF143/ZFP143 depletion system to study its direct consequences on chromatin looping and gene transcription. The effects of ZNF143/ZFP143 depletion are inconsistent with it being a looping factor, which we further confirmed by systematic analysis of previous studies. However, degradation of ZNF143/ZFP143 led to the down-regulation of hundreds of its targets, which were found to be enriched in nuclear-encoded mitochondrial genes. By studying the consequences of ZNF143/ZFP143 loss in monoculture and in an in vitro embryonic development model, we establish ZNF143/ZFP143 as a conserved transcriptional regulator of cell proliferation and differentiation by modulating mitochondrial functions.

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The Chromatin-Looping Factor ZNF143 Engages at Looping Promoters to Favor the Estrogen Response in Breast Cancer (ChIP-seq)

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ZNF143 deletion alters enhancer/promoter looping and CTCF/cohesin geometry [HiChIP]

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