Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA379617 | ENA |
REPOSITORIES: ENA
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Project description:ZBTB48 is both a vertebrate telomere-binding protein and a transcriptional activator
| PRJNA379618 | ENA
Project description:ZBTB48 is both a vertebrate telomere-binding protein and a transcriptional activator [RNA-seq]
| PRJNA379623 | ENA
Project description:Telomeres constitute the ends of linear chromosomes and together with the shelterin complex form a structure essential for genome maintenance and stability. In addition to the constitutive binding of the shelterin complex, other direct, yet more transient interactions are mediated by the CST complex and HOT1, while subtelomeric variant repeats are recognized by NR2C/F transcription factors. Recently, the Kruppel-like zinc finger protein ZBTB48 has been described as a novel telomere-associated factor in the vertebrate lineage. Here, we show that ZBTB48 binds directly both to telomeric as well as to subtelomeric variant repeat sequences. ZBTB48 is found at telomeres of human cancer cells regardless of the mode of telomere maintenance and it acts as a negative regulator of telomere length. In addition to its telomeric function, we demonstrate through a combination of RNAseq, ChIPseq and expression proteomics experiments that ZBTB48 acts as a transcriptional activator on a small set of target genes, including mitochondrial fission process 1 (MTFP1). This discovery places ZBTB48 at the interface of telomere length regulation, transcriptional control and mitochondrial metabolism.
2017-05-11 | PXD006074 | Pride
Project description:<p>Gene expression is a biological process regulated at different molecular levels, including chromatin accessibility, transcription, and RNA maturation and transport. In addition, these regulatory mechanisms have strong links with cellular metabolism. Here we present a multi-omics dataset that captures different aspects of this multi-layered process in yeast. We obtained RNA-seq, metabolomics, and H4K12Ac ChIP-seq data for wild-type and mip6delta strains during a heat-shock time course. Mip6 is an RNA-binding protein that contributes to RNA export during environmental stress and is informative of the contribution of post-transcriptional regulation to control cellular adaptations to environmental changes. The experiment was performed in quadruplicate, and the different omics measurements were obtained from the same biological samples, which facilitates the integration and analysis of data using covariance-based methods. We validate our dataset by showing that ChIP-seq, RNA-seq and metabolomics signals recapitulate existing knowledge about the response of ribosomal genes and the contribution of trehalose metabolism to heat stress.</p>
2020-02-14 | MTBLS1320 | MetaboLights
Project description:The TTAGGG motif is common to two seemingly unrelated dimensions of chromatin function M-^V the vertebrate telomere repeat and the promoter regions of many Schizosaccharomyces pombe genes, including all of those encoding canonical histones. The essential S. pombe protein Teb1 contains two Myb-like DNA binding domains related to those found in telomere proteins and binds the human telomere repeat sequence TTAGGG. Here we analyze Teb1 binding throughout the genome and the consequences of reduced Teb1 function. ChIP on chip analysis reveals robust Teb1 binding at many promoters, notably including all of those controlling canonical histone gene expression. A hypomorphic allele, teb1-1, confers reduced binding and reduced levels of histone transcripts. teb1-1 cells also show severe defects in the G1-arrest-associated clipping of histones, most likely due to a role for Teb1 in promoting expression of the protease Isp6. Prompted by previously suggested connections between histone expression and centromere identity, we examined localization of the centromeric histone H3 variant Cnp1 and found reduced centromeric binding along with reduced centromeric silencing. These data identify Teb1 as a master regulator of histone levels and centromere identity.
2013-08-14 | E-MTAB-1253 | biostudies-arrayexpress
Project description:<p>Hepatoblastoma (HB) is the most common pediatric liver tumor, affecting mostly children under 3 years of age. This rare tumor represents 1% of all pediatric cancers. Genetic studies have shown that HB is characterized by high frequency mutations of the CTNNB1 gene encoding beta-catenin (around 75%) and relative genomic stability. Here we have analyzed the transcriptional profile of 21 HBs compared to matched non-tumor livers by Cap Analysis of Gene Expression (CAGE), which provides accurate and quantitative profiling of all transcripts. CAGE analysis revealed strong upregulation of known Wnt target coding genes in most tumors analyzed, consistent with previous transcriptomic studies. To better define the Wnt-dependent transcriptional landscape of HB, we integrated CAGE data with TCF4 ChIP-seq data from a CTNNB1-mutated cancer cell line and with the FANTOM5 genomic coordinates of TCF/LEF binding motifs. Both TCF/LEF binding motifs and ChIP-seq peaks were strongly enriched in the immediate upstream region, not only for protein-coding genes, but also for non-coding transcripts. Among the selected 112 top Wnt target genes at FDR<1.0E-6 and fold change>8, we found clear over-representation (66%) of distant transcription start sites (TSSs) representing lncRNAs and enhancer RNAs, which raises the question of their role in HB pathogenesis. Analysis of the 112 promoters using CAGEd-oPOSSUM confirmed the predominant involvement of Tcf/Lef transcription factors, together with HNF4G, GATA2, Sox3 and Ets-related genes. Finally, the 112 Wnt target signature defined 3 tumor subclasses, T1, T2 and T3, characterized by progressive alteration of the non-coding part of the transcriptome and significant differences in clinical behavior.</p>
| phs001433 | dbGaP
Project description:Repressor-activator protein 1 (scRap1) is the major binding activity at Saccharomyces cerevisiae telomeres, with roles in telomere length regulation and establishment of subtelomeric silencing by recruiting the Sir proteins. scRap1 also acts as a transcription factor controlling the expression of ribosomal proteins and glycolytic enzymes. A homolog of scRap1 exist in mammals, Rap1 (also known as Terf2ip), however, its roles in telomere biology and transcriptional regulation are largely unknown. We have employed microarrays to obtain gene expression signatures related to Rap1-deleted mice when compared to the wild-type.
2010-07-10 | GSE19011 | GEO
Project description:Accurate control of tissue-specific gene expression plays a pivotal role in heart development. However, few cardiac transcriptional enhancers have thus far been identified. Extreme non-coding sequence conservation successfully predicts enhancers active in many tissues, but fails to identify substantial numbers of enhancers active in the heart. We used ChIP-seq with the enhancer-associated protein p300 from mouse embryonic heart tissue to identify over three thousand candidate heart enhancers genome-wide. In contrast to other studied tissues at this time-point, most candidate heart enhancers are not deeply conserved in vertebrate evolution. Nevertheless, the testing of 130 candidate regions in a transgenic mouse assay revealed that most of them reproducibly function as enhancers active in the heart, irrespective of their degree of evolutionary constraint. These results provide evidence for tissue-dependent differences in evolutionary constraint of enhancers acting through the transcriptional co-activator p300 at this time-point, and identify a large population of poorly conserved heart enhancers. Examination of p300 binding in embryonic stage 11.5 mouse heart and midbrain
2010-08-22 | E-GEOD-22549 | biostudies-arrayexpress
Project description:Accumulating evidence suggests important roles of RNAs interacting with genomic regions in the regulation of genome functions including X chromosome inactivation and gene expression. However, no method to identify RNAs interacting with a given genomic region in a non-biased manner has been reported. Here, we used engineered DNA-binding molecule-mediated chromatin immunoprecipitation (enChIP) combined with the RNA-Seq analysis (enChIP-RNA-Seq) to perform non-biased search of RNAs interacting with telomeres. In enChIP-RNA-Seq, the target genomic regions are captured with an engineered DNA-binding molecule such as a TAL protein. Subsequently, RNAs are purified and subjected to the RNA-Seq analysis. The detected RNAs contained known telomere-binding RNAs including telomerase RNA and Cajal body-specific RNAs. In addition, we detected many novel telomere-binding RNAs. We confirmed binding of candidate RNAs to telomeres by the enChIP-RT-PCR analysis. Identified novel telomere-binding RNAs may play important roles in telomere functions. In addition, our results suggest that enChIP-RNA-Seq analysis would be useful for identification of RNAs interacting with specific genomic regions. RNAs associated with telomeres were identified by using the enChIP technology combined with deep sequencing using Illumina Miseq. Briefly, to isolate telomeres, a TAL protein, Telomere-TAL (Tel-TAL), recognizing a 19-bp sequence containing an array of TTAGGG (telomere repeats) was fused with 3xFLAG tag and NLS (3xFN-Tel-TAL) and LexA protein (3xFNLDD)11 were expressed in a mouse hematopoietic cell line, Ba/F3, respectively. The cells were crosslinked with formaldehyde, and crosslinked chromatin was fragmented by sonication. Subsequently, chromatin complexes containing 3xFN-Tel-TAL or 3xFNLDD were immunoprepicitated with anti-FLAG M2 Ab. Supplementary URL: http://www.nature.com/srep/2013/131108/srep03171/full/srep03171.html
2015-04-16 | E-GEOD-60425 | biostudies-arrayexpress
Project description:Estrogen Receptor alpha (ERα) is a key driver of most breast cancers, and it is the target of endocrine therapies used in the clinic to treat women with ERα positive (ER+) breast cancer. The two methods ChIP-seq (chromatin immunoprecipitation coupled with deep sequencing) and RIME (Rapid Immunoprecipitation of Endogenous Proteins) have greatly improved our understanding of ERα function during breast cancer progression and in response to anti-estrogens. A critical component of both ChIP-seq and RIME protocols is the antibody that is used to pull down the bait protein. To date, most of the ChIP-seq and RIME experiments for the study of ERα have been performed using the sc-543 antibody from Santa Cruz Biotechnology. However, this antibody has been discontinued, thereby severely impacting the study of ERα in normal physiology as well as diseases such as breast cancer and ovarian cancer. Here, we compare the sc-543 antibody with other commercially available antibodies, and we show that 06-935 (EMD Millipore) and ab3575 (Abcam) antibodies can successfully replace the sc-543 antibody for ChIP-seq and RIME experiments.
2019-03-21 | PXD012930 | Pride