Transposable elements drive the evolution of metazoan zinc finger genes
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ABSTRACT:
ORGANISM(S): Danio rerio
PROVIDER: GSE229157 | GEO | 2023/04/10
REPOSITORIES: GEO
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Project description:The largest and most diverse class of eukaryotic transcription factors contain Cys2-His2 zinc fingers (C2H2-ZFs). Here, we have explored the diversity of sequence preferences of C2H2-ZF proteins in non-metazoan organisms using PBM experiments.
2017-07-10 | GSE73117 | GEO
Project description:With over 700 members, the Cys2-His2 zinc finger proteins (C2H2-ZNFs) constitute the largest class of DNA-binding transcription factors (TFs), yet remain largely uncharacterized1. Although certain family members, including GTF3A, WT1 and CTCF, have been shown to bind both DNA and RNA2,3, the extent to which C2H2-ZNFs interact with – and regulate – RNA-associated processes is not known. Here, we utilized UV crosslinking and immunoprecipitation (CLIP) and found that 148 of 150 C2H2-ZNFs that we analyzed bound directly to RNA in human cells. By integrating data from new individual nucleotide resolution RNA-binding maps for 50 of these C2H2-ZNFs with data from chromatin immunoprecipitation sequencing (ChIP-seq), protein-protein interaction, and RNA-seq experiments4, we observe that the RNA-binding profiles of C2H2-ZNFs are generally distinct from their DNA-binding preferences and that they regulate a variety of post-transcriptional processes, including pre-mRNA splicing, cleavage and polyadenylation, and m6A modification of mRNA. Our results thus substantially expand the cellular repertoire of RBPs by systematically defining RNA targets and regulatory roles of C2H2-ZNFs, and they provide a valuable resource for elucidating crosstalk between transcriptional and post-transcriptional regulatory programs.
2024-09-09 | GSE230844 | GEO
Project description:With over 700 members, the Cys2-His2 zinc finger proteins (C2H2-ZNFs) constitute the largest class of DNA-binding transcription factors (TFs), yet remain largely uncharacterized1. Although certain family members, including GTF3A, WT1 and CTCF, have been shown to bind both DNA and RNA2,3, the extent to which C2H2-ZNFs interact with – and regulate – RNA-associated processes is not known. Here, we utilized UV crosslinking and immunoprecipitation (CLIP) and found that 148 of 150 C2H2-ZNFs that we analyzed bound directly to RNA in human cells. By integrating data from new individual nucleotide resolution RNA-binding maps for 50 of these C2H2-ZNFs with data from chromatin immunoprecipitation sequencing (ChIP-seq), protein-protein interaction, and RNA-seq experiments4, we observe that the RNA-binding profiles of C2H2-ZNFs are generally distinct from their DNA-binding preferences and that they regulate a variety of post-transcriptional processes, including pre-mRNA splicing, cleavage and polyadenylation, and m6A modification of mRNA. Our results thus substantially expand the cellular repertoire of RBPs by systematically defining RNA targets and regulatory roles of C2H2-ZNFs, and they provide a valuable resource for elucidating crosstalk between transcriptional and post-transcriptional regulatory programs.
2024-09-09 | GSE230845 | GEO
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
Project description:Half of all human transcription factors use C2H2 zinc finger domains to specify site-specific DNA binding and yet very little is known about their role in gene regulation. Based on in vitro studies, a zinc finger code has been developed that predicts a binding motif for a particular zinc finger factor (ZNF). However, very few studies have performed genome-wide analyses of ZNF binding patterns and thus it is not clear if the binding code developed in vitro will be useful for identifying target genes of a particular ZNF. We performed genome-wide ChIP-seq for ZNF263, a C2H2 ZNF that contains 9 finger domains, a KRAB repression domain, and a SCAN domain and identified more than 5000 binding sites in K562 cells. Our results suggest that ZNF263 binds to a 24 nt site which differs from the motif predicted by the zinc finger code in several positions. Interestingly, many of the ZNF263 binding sites are located within the transcribed region of the target gene. Although ZNFs containing a KRAB domain are thought to function mainly as transcriptional repressors, many of the ZNF263 target genes are expressed at high levels. To address the biological role of ZNF263, we identified genes whose expression was altered by treatment of cells with ZNF263-specific siRNAs. Our results suggest that ZNF263 can have both positive and negative effects on transcriptional regulation of its target genes. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf Examination of ZNF263 ChIP-seq in K562 cells.
2009-12-03 | E-GEOD-19235 | biostudies-arrayexpress
Project description:Cys2His2 (C2H2)-type zinc finger (ZNF) is one of the most common DNA-binding motif and plays a major role as transcription factors, which encoded by 2% of human genes. C2H2 type ZNFs are reported as proteins of great versatility, such as regulation of differentiation, development, metabolism, cell survival, apoptosis, and autophagy. To uncover ZNF322A-mediated functional network, we applied phosphopeptide enrichment and isobaric labeling strategies with MS-based proteomics, and identified 2754 phosphorylation sites on 976 phosphoproteins.
2021-09-08 | PXD015936 | Pride
Project description:This SuperSeries is composed of the SubSeries listed below. Cys2-His2 zinc finger (C2H2-ZF) proteins represent the largest class of putative human transcription factors (TFs). However, it is unknown whether most C2H2-ZFs even bind DNA, or what sequences they bind. Using a combination of bacterial one-hybrid (B1H) assays, protein-binding microarrays (PBMs), and ChIP-seq, we have found that most natural C2H2-ZFs bind DNA both in vitro and in vivo. This SuperSeries contains the data for identification of C2H2-ZF binding preferences using these three approaches. Refer to individual Series
2015-02-17 | E-GEOD-52523 | biostudies-arrayexpress
Project description:Half of all human transcription factors use C2H2 zinc finger domains to specify site-specific DNA binding and yet very little is known about their role in gene regulation. Based on in vitro studies, a zinc finger code has been developed that predicts a binding motif for a particular zinc finger factor (ZNF). However, very few studies have performed genome-wide analyses of ZNF binding patterns and thus it is not clear if the binding code developed in vitro will be useful for identifying target genes of a particular ZNF. We performed genome-wide ChIP-seq for ZNF263, a C2H2 ZNF that contains 9 finger domains, a KRAB repression domain, and a SCAN domain and identified more than 5000 binding sites in K562 cells. Our results suggest that ZNF263 binds to a 24 nt site which differs from the motif predicted by the zinc finger code in several positions. Interestingly, many of the ZNF263 binding sites are located within the transcribed region of the target gene. Although ZNFs containing a KRAB domain are thought to function mainly as transcriptional repressors, many of the ZNF263 target genes are expressed at high levels. To address the biological role of ZNF263, we identified genes whose expression was altered by treatment of cells with ZNF263-specific siRNAs. Our results suggest that ZNF263 can have both positive and negative effects on transcriptional regulation of its target genes.
2009-11-24 | GSE19146 | GEO
Project description:Zinc finger (ZnF) domains are widespread RNA-binding domains, recognizing single stranded and double stranded RNAs. Together with other RNA-binding domains, ZnFs enhance the affinity and specificity of RNA-binding proteins (RBPs). The ZnF-containing RBP Roquin controls mRNA decay by recognizing stem-loop elements in the 3'-UTR of its target mRNAs. Stem-loop elements are bound in a shape-specific manner by the unique ROQ domain with nanomolar affinity. The ZnF was suggested to play an essential role in RNA decay by Roquin. However, its RNA motif preference was not investigated so far. Here, we use RBNS to elucidate the RNA binding preference of the isolated Roquin-1 ZnF domain. We find that the ZnF preferentially recognizes single-stranded AU-rich elements (ARE).
2024-03-21 | GSE253536 | GEO
Project description:Here, we report that ATRX co-localizes with the H3K9-methyl transferase SETDB1 (also known as ESET), the co-repressor TRIM28 (also known as KAP1), and the transcription factor ZNF274 at 3’ exons of Zinc Finger Genes (ZNFs) containing an atypical H3K9me3/H3K36me3 chromatin signature. Disruption of ATRX and ZNF274 leads to a significant reduction of H3K9me3, particularly at the 3’ ZNF exons and other atypical chromatin regions, higher percentages of DNA damage, and defects in cell cycle. Taken together, our studies suggest that ATRX binds the 3’ exons of ZNFs to maintain genomic stability through the regulation of their H3K9me3 levels
2016-04-05 | GSE70920 | GEO