Similar Datasets
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: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:BACKGROUND: A recent study by Tadepally et al. describes the clustering of zinc finger (ZF) genes in the human genome and traces their evolutionary history among several placental mammals with complete or draft genome sequences. One of the main conclusions from the paper is that there is a dramatic rate of gene duplication and gene loss, including the surprising result that 118 human ZF genes are absent in chimpanzee. The authors also present evidence concerning the ancestral order in which the ZF-associated KRAB and SCAN domains were recruited to ZF proteins. RESULTS: Based on our analysis of two of the largest human ZF gene clusters, we find that nearly all of the human genes have plausible orthologs in chimpanzee. The one exception may be a result of the incomplete sequence coverage in the draft chimpanzee genome. The discrepancy in gene content analysis may result from the authors' dependence on the preliminary NCBI gene prediction set for chimpanzee, which appears to either fail to predict or to mispredict many chimpanzee ZF genes. Similar problems may affect the authors' interpretation of the more divergent dog, mouse, and rat ZF gene complements. In addition, we present evidence that the KRAB domain was recruited to ZF genes before the SCAN domain, rather than the reverse as the authors suggest. This discrepancy appears to result from the fact that the SCAN domain did indeed arise before the KRAB domain but is present only in non-ZF genes until a much later date. CONCLUSION: When comparing gene content among species, especially when using draft genome assemblies, dependence on preliminary gene prediction sets can be seriously misleading. In such studies, genic sequences must be identified in a manner that is as independent as possible of prediction sets. In addition, we present evidence that provides a more parsimonious explanation for the large proportion of mammalian KRAB-ZF genes without a SCAN domain.
| S-EPMC2667407 | biostudies-literature
Project description:C2H2 zinc finger (C2H2-ZNF) genes are one of the largest and most complex gene super-families in metazoan genomes, with hundreds of members in the human and mouse genome. The ongoing investigation of this huge gene family requires computational support to catalog genotype phenotype comparisons of C2H2-ZNF genes between related species and finally to extend the worldwide knowledge on the evolution of C2H2-ZNF genes in general. Here, we systematically collected all the C2H2-ZNF genes in the human and mouse genome and constructed a database named SysZNF to deposit available datasets related to these genes. In the database, each C2H2-ZNF gene entry consists of physical location, gene model (including different transcript forms), Affymetrix gene expression probes, protein domain structures, homologs (and synteny between human and mouse), PubMed references as well as links to relevant public databases. The clustered organization of the C2H2-ZNF genes is highlighted. The database can be searched using text strings or sequence information. The data are also available for batch download from the web site. Moreover, the graphical gene model/protein view system, sequence retrieval system and some other tools embedded in SysZNF facilitate the research on the C2H2 type ZNF genes under an integrative view. The database can be accessed from the URL http://epgd.biosino.org/SysZNF.
| S-EPMC2686507 | biostudies-literature
Project description:C2H2 zinc finger proteins represent the largest and most enigmatic class of human transcription factors. Their C2H2-ZF arrays are highly variable, indicating that most will have unique DNA binding motifs. However, most of the binding motifs have not been directly determined. In addition, little is known about whether or how these proteins regulate transcription. Most of the ∼700 human C2H2-ZF proteins also contain at least one KRAB, SCAN, BTB, or SET domain, suggesting that they may have common interacting partners and/or effector functions. Here, we report a multifaceted functional analysis of 131 human C2H2-ZF proteins, encompassing DNA binding sites, interacting proteins, and transcriptional response to genetic perturbation. We confirm the expected diversity in DNA binding motifs and genomic binding sites, and provide motif models for 78 previously uncharacterized C2H2-ZF proteins, most of which are unique. Surprisingly, the diversity in protein-protein interactions is nearly as high as diversity in DNA binding motifs: Most C2H2-ZF proteins interact with a unique spectrum of co-activators and co-repressors. Thus, multiparameter diversification likely underlies the evolutionary success of this large class of human proteins.
| S-EPMC5131825 | biostudies-literature
Project description:The emergence of whole-genome assays has initiated numerous genome-wide studies of transcription factor localizations at genomic regulatory elements (enhancers, promoters, silencers, and insulators), as well as facilitated the uncovering of some of the key principles of chromosomal organization. However, the proteins involved in the formation and maintenance of the chromosomal architecture and the organization of regulatory domains remain insufficiently studied. This review attempts to collate the available data on the abundant but still poorly understood family of proteins with clusters of the C2H2 zinc finger domains. One of the best known proteins of this family is a well conserved protein known as CTCF, which plays a key role in the establishment of the chromosomal architecture in vertebrates. The distinctive features of C2H2 zinc finger proteins include strong and specific binding to a long and unique DNA recognition target sequence and rapid expansion within various animal taxa during evolution. The reviewed data support a proposed model according to which many of the C2H2 proteins have functions that are similar to those of the CTCF in the organization of the chromatin architecture.
| S-EPMC5509000 | biostudies-literature
Project description:The C2H2-type zinc finger protein ZNF764 acts as an enhancer for several steroid hormone receptors, and haploinsufficiency of this gene may be responsible for tissue resistance to multiple steroid hormones including glucocorticoids observed in a patient with 16p11.2 microdeletion. We examined genome-wide regulatory actions of ZNF764 on the glucocorticoid receptor (GR) in HeLa cells as a model system. ZNF764- and GR-binding sites demonstrated similar distribution in various genomic features. They positioned predominantly around 50-500?kbs from the transcription start sites of their nearby genes, and were closely localized with each other, overlapping in ~37% of them. ZNF764 demonstrated differential on/off effects on GR-binding and subsequent mRNA expression: some genes were highly dependent on the presence/absence of ZNF764, but others were not. Pathway analysis revealed that these 3 gene groups were involved in distinct cellular activities. ZNF764 physically interacted with GR at ligand-binding domain through its KRAB domain, and both its physical interaction to GR and zinc finger domain appear to be required for ZNF764 to regulate GR transcriptional activity. Thus, ZNF764 is a cofactor directing GR transcriptional activity toward specific biologic pathways by changing GR binding and transcriptional activity on the glucocorticoid-responsive genes.
| S-EPMC5282477 | biostudies-other
Project description:A ZAS gene encodes a large protein with two separate C2H2 zinc finger pairs that independently bind to specific DNA sequences, including the kappaB motif. Three paralogous mammalian genes, ZAS1, ZAS2, and ZAS3, and a related Drosophila gene, Schnurri, have been cloned and characterized. The ZAS genes encode transcriptional proteins that activate or repress the transcription of a variety of genes involved in growth, development, and metastasis. In addition, ZAS3 associates with a TNF receptor-associated factor to inhibit NF-kappaB- and JNK/ SAPK-mediated signaling of TNF-alpha. Genetic experiments show that ZAS3 deficiency leads to proliferation of cells and tumor formation in mice. The data suggest that ZAS3 is important in controlling cell growth, apoptosis, and inflammation. The potent vasoactive hormone endothelin and transcription factor AP2 gene families also each consist of three members. The ZAS, endothelin, and transcription factor AP2 genes form several linkage groups. Knowledge of the chromosomal locations of these genes provides valuable clues to the evolution of the vertebrate genome.
| S-EPMC5977514 | biostudies-literature
Project description:Cessation of transcriptional activity is a hallmark of cell division. Many biochemical pathways have been shown and proposed over the past few decades to explain the silence of this phase. In particular, many individual transcription factors have been shown to be inactivated by phosphorylation. In this report, we show the simultaneous phosphorylation and mitotic redistribution of a whole class of modified transcription factors. C(2)H(2) zinc finger proteins (ZFPs) represent the largest group of gene expression regulators in the human genome. Despite their diversity, C(2)H(2) ZFPs display striking conservation of small linker peptides joining their adjacent zinc finger modules. These linkers are critical for DNA binding activity. It has been proposed that conserved phosphorylation of these linker peptides could be a common mechanism for the inactivation of the DNA binding activity of C(2)H(2) ZFPs, during mitosis. Using a novel antibody, raised against the phosphorylated form of the most conserved linker peptide sequence, we are able to visualize the massive and simultaneous mitotic phosphorylation of hundreds of these proteins. We show that this wave of phosphorylation is tightly synchronized, starting in mid-prophase right after DNA condensation and before the breakdown of the nuclear envelope. This global phosphorylation is completely reversed in telophase. In addition, the exclusion of the phospho-linker signal from condensed DNA clearly demonstrates a common mechanism for the mitotic inactivation of C(2)H(2) ZFPs.
| S-EPMC3233627 | biostudies-literature
Project description:Transcription factors (TFs) are biological regulators of gene function in response to various internal and external stimuli. C2H2 zinc finger proteins (C2H2-ZFPs) are a large family of TFs that play crucial roles in plant growth and development, hormone signalling and response to biotic and abiotic stresses. While C2H2-ZFPs have been well characterized in many model and crop plants, they are yet to be ascertained in the evolutionarily important C3 plant Dichanthelium oligosanthes (Heller's rosette grass). In the present study, we report 32 C2H2-ZF genes (DoZFs) belonging to three different classes-Q type, C-type and Z-type based on structural elucidation and phylogenetic analysis. Sequence comparisons revealed paralogs within the DoZFs and orthologs among with rice ZF genes. Motif assignment showed the presence of the distinctive C2H2-ZF conserved domain "QALGGH" in these proteins. Cis-element analysis indicated that majority of the predicted C2H2-ZFPs are associated with hormone signalling and abiotic stress responses. Further, their role in nucleic acid binding and transcriptional regulation was also observed using predicted functional assignment. Thus, we report an overview of the C2H2-ZF gene family in D. oligosanthes that could serve as the basis for future experimental studies on isolation and functional implication of these genes in different biological mechanism of C3 plants.
| S-EPMC6859702 | biostudies-literature