Similar Datasets
Project description:The Zinc finger and SCAN domain containing 4 (ZSCAN4) protein, expressed transiently in pluripotent stem cells, gametes, and early embryos, extends telomeres, enhances genome stability, and improves karyotypes in mouse embryonic stem (mES) cells. To gain insights into the mechanism of ZSCAN4 function, we identified genome-wide binding sites of endogenous ZSCAN4 protein using ChIP-seq technology in mouse and human ES cells, where the expression of endogenous ZSCAN4 was induced by treating cells with retinoic acids or by overexpressing DUX4. We revealed that both mouse and human ZSCAN4 bind to the TGCACAC motif located in CA/TG microsatellite repeats, which are known to form unstable left-handed duplexes called Z-DNA that can induce double-strand DNA breaks and mutations. These ZSCAN4 binding sites are mostly located in intergenic and intronic regions of the genomes. By generating ZSCAN4 knockout in human ES cells, we showed that ZSCAN4 does not seem to be involved in transcriptional regulation. We also found that ectopic expression of mouse ZSCAN4 enhances the suppression of chromatin at ZSCAN4-binding sites. These results together suggest that some of the ZSCAN4 functions are mediated by binding to the error-prone regions in mouse and human genomes.
| S-EPMC10785592 | biostudies-literature
Project description:The Zinc finger and SCAN domain containing 4 (Zscan4) protein, expressed transiently in pluripotent stem cells as well as in gamete and embryonic development, regulates genome stability in addition to telomere elongation and karyotype correction in mouse ES cells. However, the mechanism underlying Zscan4’s ability to counter the toxic effects of DNA/chromatin remodeling is not fully understood. In this study, we used ChIP-seq technology with Zscan4 antibodies to identify genome-wide binding sites in mouse and human ES cells. We discovered that both mouse and human Zscan4 bind to specific simple sequence repeats, (TG/CA)n, that have a propensity to induce genomic instability through a left-handed helix and stem-loop structure. Furthermore, we found that Zscan4 removes active histone marks from (TG/CA)n regions to maintain the closed/inactive chromatin state. These results demonstrate that Zscan4 protects unstable genomic regions by directing chromatin condensation.
2024-01-25 | GSE243626 | GEO
Project description:The Zinc finger and SCAN domain containing 4 (Zscan4) protein, expressed transiently in pluripotent stem cells as well as in gamete and embryonic development, regulates genome stability in addition to telomere elongation and karyotype correction in mouse ES cells. However, the mechanism underlying Zscan4’s ability to counter the toxic effects of DNA/chromatin remodeling is not fully understood. In this study, we used ChIP-seq technology with Zscan4 antibodies to identify genome-wide binding sites in mouse and human ES cells. We discovered that both mouse and human Zscan4 bind to specific simple sequence repeats, (TG/CA)n, that have a propensity to induce genomic instability through a left-handed helix and stem-loop structure. Furthermore, we found that Zscan4 removes active histone marks from (TG/CA)n regions to maintain the closed/inactive chromatin state. These results demonstrate that Zscan4 protects unstable genomic regions by directing chromatin condensation.
2024-01-25 | GSE243627 | GEO
Project description:ZSCAN4-binding motif - TGCACAC is conserved and enriched in CA/TG microsatellites in both mouse and human genomes
| PRJNA1019280 | ENA
Project description:ZSCAN4-binding motif - TGCACAC is conserved and enriched in CA/TG microsatellites in both mouse and human genomes [RNA-Seq]
| PRJNA1019287 | ENA
Project description:ZSCAN4-binding motif - TGCACAC is conserved and enriched in CA/TG microsatellites in both mouse and human genomes [ChIP-Seq]
| PRJNA1019288 | ENA
Project description:Microsatellites (SSRs) are ubiquitous in coding and non-coding regions of the Ebolavirus genomes. We synthetically analyzed the microsatellites in whole-genome and terminal regions of 219 Ebolavirus genomes from five species. The Ebolavirus sequences were observed with small intraspecies variations and large interspecific variations, especially in the terminal non-coding regions. Only five conserved microsatellites were detected in the complete genomes, and four of them which well base-paired to help forming conserved stem-loop structures mainly appeared in the terminal non-coding regions. These results suggest that the conserved microsatellites may be evolutionary selected to form conserved secondary structures in 5', 3' terminals of Ebolavirus genomes. It may help to understand the biological significance of microsatellites in Ebolavirus and also other virus genomes.
| S-EPMC7092875 | biostudies-literature
Project description:In the Drosophila nervous system, the glial cells missing gene (gcm) is transiently expressed in glial precursors to switch their fate from the neuronal default to glia. It encodes a novel 504-amino acid protein with a nuclear localization signal. We report here that the GCM protein is a novel DNA-binding protein and that its DNA-binding activity is localized in the N-terminal 181 amino acids. It binds with high specificity to the nucleotide sequence, (A/G)CCCGCAT, which is a novel sequence among known targets of DNA-binding proteins. Eleven such GCM-binding sequences are found in the 5' upstream region of the repo gene, whose expression in early glial cells is dependent on gcm. This suggests that the GCM protein is a transcriptional regulator directly controlling repo. We have also identified homologous genes from human and mouse whose products share a highly conserved N-terminal region with Drosophila GCM. At least one of these was shown to have DNA-binding activity similar to that of GCM. By comparing the deduced amino acid sequences of these gene products, we were able to define the "gcm motif," an evolutionarily conserved motif with DNA-binding activity. By PCR amplification, we obtained evidence for the existence of additional gcm-motif genes in mouse as well as in Drosophila. The gcm-motif, therefore, forms a family of novel DNA-binding proteins, and may function in various aspects of cell fate determination.
| S-EPMC26236 | biostudies-literature
Project description:Piwi-interacting RNAs (piRNAs) fulfill a critical, conserved role in defending the genome against foreign genetic elements. In many organisms, piRNAs appear to be derived from processing of a long, polycistronic RNA precursor. Here, we establish that each Caenorhabditis elegans piRNA represents a tiny, autonomous transcriptional unit. Remarkably, the minimal C. elegans piRNA cassette requires only a 21 nucleotide (nt) piRNA sequence and an ?50 nt upstream motif with limited genomic context for expression. Combining computational analyses with a novel, in vivo transgenic system, we demonstrate that this upstream motif is necessary for independent expression of a germline-enriched, Piwi-dependent piRNA. We further show that a single nucleotide position within this motif directs differential germline enrichment. Accordingly, over 70% of C. elegans piRNAs are selectively expressed in male or female germline, and comparison of the genes they target suggests that these two populations have evolved independently. Together, our results indicate that C. elegans piRNA upstream motifs act as independent promoters to specify which sequences are expressed as piRNAs, how abundantly they are expressed, and in what germline. As the genome encodes well over 15,000 unique piRNA sequences, our study reveals that the number of transcriptional units encoding piRNAs rivals the number of mRNA coding genes in the C. elegans genome.
| S-EPMC3597512 | biostudies-other
Project description:Lateral inhibition is one of the key functions of Notch signaling during animal development. In the proneural clusters that give rise to Drosophila mechanosensory bristles, Delta (Dl) ligand in the sensory organ precursor (SOP) cell is targeted for ubiquitination by the E3 ligase Neuralized (Neur), resulting in activation of Dl's capacity to signal to the Notch receptor on neighboring cells. The cells that receive this signal activate a genetic program that suppresses their SOP fate potential, insuring that only a single SOP develops within each cluster. Using multiple lines of investigation, we provide evidence that members of the Bearded family of proteins (BFMs) inhibit Dl activation in non-SOP cells by binding to Neur and preventing it from interacting with Dl. We show that this activity of BFMs is dependent on the conserved NXXN motif, and report the unexpected finding that several BFMs include multiple functional copies of this motif. We find that a conserved NXXN motif in the intracellular domain of Dl is responsible for its interaction with Neur, indicating direct competition between Dl and BFMs for binding to Neur, and we show that Neur-dependent endocytosis of Dl requires the integrity of its NXXN motif. Our results illuminate the mechanism of an important regulatory event in Notch signaling that appears to be conserved between insects and crustaceans.
| S-EPMC2793682 | biostudies-literature