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Integrated multi-omics analysis of zinc finger proteins uncovers roles in RNA regulation [RNA-seq]

ABSTRACT: RNA interactome studies have revealed that hundreds of zinc finger proteins (ZFPs) are candidate RNA-binding proteins (RBPs), despite being annotated as DNA-interacting transcription factors. The RNA substrates of ZFPs and the functional significance of their potential roles as DNA- and RNA-binding proteins (DRBPs) remain largely uncharacterized. Here we present a systematic multi-omics analysis of the DNA and RNA binding targets and regulatory roles of more than 100 ZFPs representing 37 zinc finger families. We show that multiple ZFPs are novel regulators of RNA splicing, polyadenylation, or stability. The examined ZFPs show widespread sequence-specific RNA binding ability and preferentially bind proximal to transcription start sites. Additionally, several ZFPs are DRBPs that bind their targets at both the DNA and RNA levels. We highlight ZNF277, a C2H2 ZFP that binds thousands of RNA targets and acts as a multi-functional RBP. We also show that ZNF473 is a DRBP that regulates the expression and splicing of cell cycle genes. Our results reveal diverse roles for ZFPs in transcriptional and post-transcriptional gene regulation, shedding light on a large class of under-studied RBPs.

ORGANISM(S): Homo sapiens

PROVIDER: GSE277160 | GEO | 2024/09/20

REPOSITORIES: GEO

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Integrated multi-omics analysis of zinc finger proteins uncovers roles in RNA regulation [RBNS]

Project description:RNA interactome studies have revealed that hundreds of zinc finger proteins (ZFPs) are candidate RNA-binding proteins (RBPs), despite being annotated as DNA-interacting transcription factors. The RNA substrates of ZFPs and the functional significance of their potential roles as DNA- and RNA-binding proteins (DRBPs) remain largely uncharacterized. Here we present a systematic multi-omics analysis of the DNA and RNA binding targets and regulatory roles of more than 100 ZFPs representing 37 zinc finger families. We show that multiple ZFPs are novel regulators of RNA splicing, polyadenylation, or stability. The examined ZFPs show widespread sequence-specific RNA binding ability and preferentially bind proximal to transcription start sites. Additionally, several ZFPs are DRBPs that bind their targets at both the DNA and RNA levels. We highlight ZNF277, a C2H2 ZFP that binds thousands of RNA targets and acts as a multi-functional RBP. We also show that ZNF473 is a DRBP that regulates the expression and splicing of cell cycle genes. Our results reveal diverse roles for ZFPs in transcriptional and post-transcriptional gene regulation, shedding light on a large class of under-studied RBPs.

2024-09-20 | GSE277047 | GEO

Integrated multi-omics analysis of zinc finger proteins uncovers roles in RNA regulation [SLAM-Seq]

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Integrated multi-omics analysis of zinc finger proteins uncovers roles in RNA regulation [eCLIP]

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Integrated multi-omics analysis of zinc finger proteins uncovers roles in RNA regulation [Cut&Run]

Project description:RNA interactome studies have revealed that hundreds of zinc finger proteins (ZFPs) are candidate RNA-binding proteins (RBPs), despite being annotated as DNA-interacting transcription factors. The RNA substrates of ZFPs and the functional significance of their potential roles as DNA- and RNA-binding proteins (DRBPs) remain largely uncharacterized. Here we present a systematic multi-omics analysis of the DNA and RNA binding targets and regulatory roles of more than 100 ZFPs representing 37 zinc finger families. We show that multiple ZFPs are novel regulators of RNA splicing, polyadenylation, or stability. ZFPs show widespread sequence-specific RNA binding ability and preferentially bind proximal to transcription start and end sites. Additionally, several ZFPs are DRBPs that bind their targets at both the DNA and RNA levels. We highlight ZNF277, a C2H2 ZFP that binds thousands of RNA targets and acts as a multi-functional RBP. We also show that ZNF473 is a DRBP that regulates the expression and splicing of cell cycle genes. Our results reveal diverse roles for ZFPs in transcriptional and post-transcriptional gene regulation, shedding light on a large class of under-studied RBPs.

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Integrated multi-omics analysis of zinc finger proteins uncovers roles in RNA regulation [Ribo-STAMP cell lines]

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Integrated multi-omics analysis of zinc finger proteins uncovers roles in RNA regulation

Project description:RNA interactome studies have revealed that hundreds of zinc-finger proteins (ZFPs) are candidate RNA-binding proteins (RBPs), yet their RNA substrates and functional significance remain largely uncharacterized. Here, we present a systematic multi-omics analysis of the DNA- and RNA-binding targets and regulatory roles of more than 100 ZFPs representing 37 zinc-finger families. We show that multiple ZFPs are previously unknown regulators of RNA splicing, alternative polyadenylation, stability, or translation. The examined ZFPs show widespread sequence-specific RNA binding and preferentially bind proximal to transcription start sites. Additionally, several ZFPs associate with their targets at both the DNA and RNA levels. We highlight ZNF277, a C2H2 ZFP that binds thousands of RNA targets and acts as a multi-functional RBP. We also show that ZNF473 is a DNA/RNA-associated protein that regulates the expression and splicing of cell cycle genes. Our results reveal diverse roles for ZFPs in transcriptional and post-transcriptional gene regulation.

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Global analysis of Drosophila Cys2-His2 zinc finger proteins reveals a multitude of novel recognition motifs and binding determinants.

Project description:Cys2-His2 zinc finger proteins (ZFPs) are the largest group of transcription factors in higher metazoans. A complete characterization of these ZFPs and their associated target sequences is pivotal to fully annotate transcriptional regulatory networks in metazoan genomes. As a first step in this process, we have characterized the DNA-binding specificities of 130 Zinc finger sets from Drosophila melanogaster using a bacterial one-hybrid system. This data set contains the DNA-binding specificities for at least one encoded ZFP from 71 unique genes and 22 alternate splice isoforms. This represents the largest block of characterized ZFPs from any organism described to date. These recognition motifs can be used to predict genomic binding sites and potential regulatory targets for these factors within the fruit fly genome. We have characterized subsets of fingers from these ZFPs to define the correct orientation and register of the zinc fingers on their defined binding sites. By correlating individual fingers with motif subsites, we can assign finger specificity throughout each ZFP. This reveals the diversity of recognition potential within the naturally-occurring zinc fingers of a single organism, where the characterized fingers can specify 47 of the 64 possible DNA triplets. To confirm the utility of our finger recognition models, we have employed subsets of Drosophila fingers in combination with an existing archive of zinc finger modules to create ZFPs with novel DNA-binding specificity. These finger combinations can be used to create novel functional Zinc Finger Nucleases for editing vertebrate genomes. Illumina sequencing of Barcoded Binding sites obtained after B1H selection of Cys2-His2 zinc finger proteins cloned as a C-terminal fusions to the omega subunit of E. coli RNA polymerase in the B1H system.

2012-12-06 | E-GEOD-42709 | biostudies-arrayexpress

Global analysis of Drosophila Cys2-His2 zinc finger proteins reveals a multitude of novel recognition motifs and binding determinants.

2012-12-06 | GSE42709 | GEO

Genome-wide analysis of differential transcription in KRAB-ZFP cluster knock-out ES cells and mouse tissues

Project description:Mammalian genomes encode several hundred Krüppel-associated box zinc finger proteins (KRAB-ZFPs) that bind DNA in a sequence-specific manner through tandem arrays of C2H2-type zinc fingers and repress transcription via KRAB-dependent recruitment of the silencing cofactor KAP1. The KRAB-ZFP family rapidly amplified and diversified in mammals by segmental gene duplications, mutations, and zinc finger rearrangements likely in response to continued transposable element invasions, but the biological functions and in vivo requirement of these proteins has gone largely unexplored. We determined the genomic binding sites of 61 murine KRAB-ZFPs and genetically deleted five large KRAB-ZFP gene clusters encoding more than 100 of the approximately 360 mouse KRAB-ZFPs. We demonstrate that most KRAB-ZFPs bind to specific retrotransposon families and that many of these retrotransposons are transcriptionally activated in KRAB-ZFP cluster KO ESCs, licensing retrotransposon-derived enhancers to activate nearby genes.

2019-06-27 | GSE115288 | GEO

Genome-wide binding patterns of murine KRAB zinc finger proteins

Project description:Mammalian genomes encode several hundred Krüppel-associated box zinc finger proteins (KRAB-ZFPs) that bind DNA in a sequence-specific manner through tandem arrays of C2H2-type zinc fingers and repress transcription via KRAB-dependent recruitment of the silencing cofactor KAP1. The KRAB-ZFP family rapidly amplified and diversified in mammals by segmental gene duplications, mutations, and zinc finger rearrangements likely in response to continued transposable element invasions, but the biological functions and in vivo requirement of these proteins has gone largely unexplored. Here we report the identification of the genome-wide binding profiles of 61 mouse KRAB-ZFPs by overexpression of epitope-tagged transgenes. We found that 51 of these KRAB-ZFPs target at least one retrotransposon group. Interestingly, evolutionary young and still active retrotransposons such as IAP and ETn elements are targeted by several KRAB-ZFPs which are mainly encoded within two gene clusters that are not conserved in any other sequenced species. This indicated that an evolutionary arms race drives the rapid expansion of KRAB-ZFP genes in order to restrict active retrotransposons.

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