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Differentially expressed zinc finger proteins during human adipogenesis

ABSTRACT: To investigate the collective role of zinc finger proteins in adipogenesis, we induced adipogenesis using human mesenchymal stem cells (MSC) and compared the gene expression profiles using human Illumina beads arrays. We performed three independent experiments of time-series analysis (0h, 1h, 12h, 24h, 2d, 4d, 6d, 9d, 12d, 15d after induction of adipogenesis) in order to comprehensively capture the dynamic profiles of transcriptome during differentiation. Statistical filtering based on Analysis of Variance (ANOVA; p-value < 0.001, FDR 5%) and Gene Ontology classification using the Human Gene Nomenclature Database (HGNC) identified 618 out of 678 zinc finger proteins (ZFPs) that were significantly expressed during adipogenesis. Moreover, 34 out of 618 genes were differentially expressed more than 2-fold up or down regulated. The K-means clustering analysis further revealed four dynamic expression patterns: one gene in early-response, seven genes in transient, twenty genes in progressively-induced and four genes in the down-regulated, demonstrating the dynamic involvement of ZFPs in the process of adipocyte differentiation and maturation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE37836 | GEO | 2012/12/01

SECONDARY ACCESSION(S): PRJNA163875

REPOSITORIES: GEO

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Differentially expressed zinc finger proteins during human adipogenesis

Project description:To investigate the collective role of zinc finger proteins in adipogenesis, we induced adipogenesis using human mesenchymal stem cells (MSC) and compared the gene expression profiles using human Illumina beads arrays. We performed three independent experiments of time-series analysis (0h, 1h, 12h, 24h, 2d, 4d, 6d, 9d, 12d, 15d after induction of adipogenesis) in order to comprehensively capture the dynamic profiles of transcriptome during differentiation. Statistical filtering based on Analysis of Variance (ANOVA; p-value < 0.001, FDR 5%) and Gene Ontology classification using the Human Gene Nomenclature Database (HGNC) identified 618 out of 678 zinc finger proteins (ZFPs) that were significantly expressed during adipogenesis. Moreover, 34 out of 618 genes were differentially expressed more than 2-fold up or down regulated. The K-means clustering analysis further revealed four dynamic expression patterns: one gene in early-response, seven genes in transient, twenty genes in progressively-induced and four genes in the down-regulated, demonstrating the dynamic involvement of ZFPs in the process of adipocyte differentiation and maturation. Total RNA obteind from 10 different time points (0h, 1h, 12h, 24h, 2d, 4d, 6d, 9d, 12d, 15d) during adipogenesis from human Mesenchymal stem cell (MSC) to Adipocyte (ADP). Adipogensis was induced by the different cocktail of chemical compunds containing human-insulin, dexamethasone, indomethacin and IBMX.

2012-12-01 | E-GEOD-37836 | biostudies-arrayexpress

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.

2019-06-27 | GSE115287 | GEO

Homo sapiens

Project description:Differentially expressed zinc finger proteins during human adipogenesis

| PRJNA163875 | ENA

Downregulation of KRAB zinc finger proteins in 5-fluorouracil resistant colorectal cancer cells

Project description:The radio-chemotherapy with 5-fluorouracil (5-FU) is the standard of care treatment for patients with locally advanced rectal cancer (LARC) but it is only effective for a third of them. The proteomic and transcriptomic response of three colorectal cancer (CRC) cell lines to 5-FU and radiation was assessed and correlated with their genetic background. The induction of a 5-FU-resistance in those cell lines negatively affects the levels of transcripts corresponding to Krüppel-associated box (KRAB)-containing zinc finger proteins (ZFPs), the largest family of transcriptional repressors. Among nearly 350 KRAB-ZFPs, almost a quarter are down-regulated after the induction of a 5-FU-resistance including a common one between the three CRC cell lines, ZNF649, whose role is still unknown. This proteomic, transcriptomic and genomic analysis of intrinsic and acquired resistance highlights possible new mechanisms involved in resistance to treatment and therefore potential new therapeutic targets to overcome this resistance.

2022-05-19 | PXD020000 | Pride

Transposable elements and their KRAB-ZFP controllers regulate gene expression in adult tissues

Project description:The tetrapod-restricted KRAB-containing zinc finger proteins (KRAB-ZFPs) are essential early embryonic controllers of transposable elements (TEs), which they repress via their cofactor KAP1 and associated effectors through histone and DNA methylation, a process thought to result in irreversible silencing. Using a target-centered functional screen, we matched several murine TEs with their cognate KRAB-ZFP. This revealed an unexpected level of granularity in their interactions, with KRAB-ZFPs recognizing TEs from more than one subfamily, TEs recruiting more than one KRAB-ZFP, and spatially and temporally differential KRAB-ZFP-mediated regulation of TEs and nearby genes. Most importantly, we discovered that the KRAB/KAP1 system controls TEs in adult tissues, in cell culture and in vivo, where they partner up to regulate the expression of cellular genes. Therefore, TEs and KRAB-ZFPs establish widely active transcription networks that regulate not only development but probably also many physiological events. Given the high degree of species-specificity of both TEs and KRAB-ZFPs, these results have important implications for studying and understanding the biology of higher vertebrates, including humans. Analysis of transcriptional profiles of KAP1 or ZFP932/Gm15446 KO cells or tissues, and ZFP932 and Gm15446 ChIPseq in murine ES and C2C12 cells.

2016-03-15 | E-GEOD-74278 | biostudies-arrayexpress

Transposable elements and their KRAB-ZFP controllers regulate gene expression in adult tissues

2016-03-15 | GSE74278 | GEO

ChIP-exo of human KRAB-ZNFs transduced in HEK 293T cells and KAP1 in hES H1 cells

Project description:Encoded in the hundreds by the human genome, KRAB-containing zinc finger proteins (KRAB-ZFPs) constitute a rapidly evolving family of transcription factors with largely undefined functions. Here, by a combination of phylogenetic and genomic approaches, we retrace the evolutionary history of KRAB-ZFP genes and define the genomic targets of their human products. Through in silico analysis of 207 vertebrate genomes and chromatin immunoprecipitation / deep sequencing characterization of 257 human KRAB-ZFPs, we identify the root of the family in an early Devonian ancestor of tetrapods, describe its diversity amongst these species, and reveal that the majority of its human members primarily recognize transposable elements. Furthermore, by dissecting the timeline and modalities of interactions between human KRAB-ZFPs and their targets, we provide evidence strongly suggesting that these proteins, rather than just engaged in an evolutionary arms race against transposable elements, exploit these invaders as regulatory platforms for the benefit of the host.

2017-03-06 | GSE78099 | GEO

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