Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA295400 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR2353004.fastq.gz | Fastqsanger.gz | |||
| SRR2353005.fastq.gz | Fastqsanger.gz | |||
| SRR2353006.fastq.gz | Fastqsanger.gz |
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Project description:Damage to the gene regulatory network governing terminal differentiation of melanocytes leads to pigmentation phenotypes and increases the risk for melanoma. Microphthalmia-associated transcription factor (MITF) directly activates expression of melanocyte differentiation effectors, and levels of MITF have been proposed to govern the melanoma phenotype. Mutations in the gene encoding Transcription Factor Activator Protein 2 alpha (TFAP2A) cause reduced pigmentation in model organisms and premature hair graying in humans, and TFAP2A expression tends to be lower in advanced melanoma tumors than in benign nevi. However, the transcriptional targets of TFAP2A in melanocytes, and the epistatic relationship of TFAP2A and MITF, have been unclear. Using microarray-based analysis of zebrafish tfap2a mutant embryos, we generated a profile of genes whose expression is Tfap2a-dependent. We conducted anti-TFAP2A chromatin immunoprecipitation followed by next-generation sequencing (ChIP-seq) in immortalized mouse melanocytes and human primary melanocytes, and discovered that TFAP2A peaks are present near the promoters of Tfap2a-dependent genes expressed in melanocytes, and also at the majority of enhancers active in melanocytes. Comparison of TFAP2A ChIP-seq data to published MITF ChIP-seq data showed that the set of genes with promoters bound by both MITF and TFAP2A is enriched for the gene ontology term “pigment cell differentiation.” Deletion analysis of one such co-bound promoter, for Transient Receptor Potential Melastatin-like 1(TRPM1), confirmed that its expression depends on the presence of MITF binding sites as previously shown, but also depends on the presence of TFAP2A binding sites. Finally, we find that mitfa and tfap2a interact genetically in zebrafish. Collectively, these results show that TFAP2A, operating in parallel with MITF, directly regulates effectors of terminal differentiation in melanocytes and melanoma.
2017-02-17 | GSE72953 | GEO
Project description:Mutations in the gene encoding transcription factor TFAP2A result in pigmentation anomalies in model organisms and premature hair graying in humans. However, the pleiotropic functions of TFAP2A and its redundantly-acting paralogs have made the precise contribution of TFAP2-type activity to melanocyte differentiation unclear. Defining this contribution may help to explain why TFAP2A expression is reduced in advanced-stage melanoma compared to benign nevi. To identify genes with TFAP2A-dependent expression in melanocytes, we profile zebrafish tissue and mouse melanocytes deficient in Tfap2a, and find that expression of a small subset of genes underlying pigmentation phenotypes is TFAP2A-dependent, including Dct, Mc1r, Mlph, and Pmel. We then conduct TFAP2A ChIP-seq in mouse and human melanocytes and find that a much larger subset of pigmentation genes is associated with active regulatory elements bound by TFAP2A. These elements are also frequently bound by MITF, which is considered the “master regulator” of melanocyte development. For example, the promoter of TRPM1 is bound by both TFAP2A and MITF, and we show that the activity of a minimal TRPM1 promoter is lost upon deletion of the TFAP2A binding sites. However, the expression of Trpm1 is not TFAP2A-dependent, implying that additional TFAP2 paralogs function redundantly to drive melanocyte differentiation, which is consistent with previous results from zebrafish. Paralogs Tfap2a and Tfap2b are both expressed in mouse melanocytes, and we show that mouse embryos with Wnt1-Cre-mediated deletion of Tfap2a and Tfap2b in the neural crest almost completely lack melanocytes but retain neural crest-derived sensory ganglia. These results suggest that TFAP2 paralogs, like MITF, are also necessary for induction of the melanocyte lineage. Finally, we observe a genetic interaction between tfap2a and mitfa in zebrafish, but find that artificially elevating expression of tfap2a does not increase levels of melanin in mitfa hypomorphic or loss-of-function mutants. Collectively, these results show that TFAP2 paralogs, operating alongside lineage-specific transcription factors such as MITF, directly regulate effectors of terminal differentiation in melanocytes. In addition, they suggest that TFAP2A activity, like MITF activity, has the potential to modulate the phenotype of melanoma cells.
2017-02-23 | GSE67555 | GEO
Project description:Introgressed variants from other species can be an important source of genetic variation because they may arise rapidly, can include multiple mutations on a single haplotype, and have often been pretested by selection in the species of origin. Although introgressed alleles are generally deleterious, several studies have reported introgression as the source of adaptive alleles-including the rodenticide-resistant variant of Vkorc1 that introgressed from Mus spretus into European populations of Mus musculus domesticus. Here, we conducted bidirectional genome scans to characterize introgressed regions into one wild population of M. spretus from Spain and three wild populations of M. m. domesticus from France, Germany, and Iran. Despite the fact that these species show considerable intrinsic postzygotic reproductive isolation, introgression was observed in all individuals, including in the M. musculus reference genome (GRCm38). Mus spretus individuals had a greater proportion of introgression compared with M. m. domesticus, and within M. m. domesticus, the proportion of introgression decreased with geographic distance from the area of sympatry. Introgression was observed on all autosomes for both species, but not on the X-chromosome in M. m. domesticus, consistent with known X-linked hybrid sterility and inviability genes that have been mapped to the M. spretus X-chromosome. Tract lengths were generally short with a few outliers of up to 2.7 Mb. Interestingly, the longest introgressed tracts were in olfactory receptor regions, and introgressed tracts were significantly enriched for olfactory receptor genes in both species, suggesting that introgression may be a source of functional novelty even between species with high barriers to gene flow.
| S-EPMC8784167 | biostudies-literature
Project description:Chip-seq analysis of immortalized melanocytes Hermes 3c and Hermes 4c derivative cell lines following lentiviral transduction of a HA-tagged MITF-M construct (pLX3xHAvar4mCherry)
2020-07-02 | GSE142014 | GEO
Project description:We use comprehensive and unsupervised transcriptome analyses to provide molecular classifications of sensory neurons in the mouse geniculate ganglion. 96 neurons were isolated on a C1 Fluodigm chip, underwent RNA-Seq, and iteratively clustered into sub-classes.
2017-10-02 | GSE102443 | GEO
Project description:Translational research is commonly performed in the C57B6/J mouse strain, chosen for its genetic homogeneity and phenotypic uniformity. Here, we evaluate the suitability of the white-footed deer mouse (Peromyscus leucopus) as a model organism for aging research, offering a comparative analysis against C57B6/J and diversity outbred (DO) Mus musculus strains. Our study includes comparisons of body composition, skeletal muscle function, and cardiovascular parameters, shedding light on potential applications and limitations of P. leucopus in aging studies. Notably, P. leucopus exhibits distinct body composition characteristics, emphasizing reduced muscle force exertion and a unique metabolism, particularly in fat mass. Cardiovascular assessments showed changes in arterial stiffness, challenging conventional assumptions and highlighting the need for a nuanced interpretation of aging-related phenotypes. Our study also highlights inherent challenges associated with maintaining and phenotyping P. leucopus cohorts. Behavioral considerations, including anxiety-induced responses during handling and phenotyping assessment, pose obstacles in acquiring meaningful data. Moreover, the unique anatomy of P. leucopus necessitates careful adaptation of protocols designed for Mus musculus. While showcasing potential benefits, further extensive analyses across broader age ranges and larger cohorts are necessary to establish the reliability of P. leucopus as a robust and translatable model for aging studies.
| S-EPMC11335981 | biostudies-literature
Project description:Hypoxia can be established under pathological conditions, such as cancer, due to the imbalance between oxygen supply and consumption. Hypoxia Inducible Transcription Factor HIF-1 mediates the physiological response to hypoxia but also regulates multiple steps of carcinogenesis. Despite its well-defined oxygen-dependent activation, many aspects of HIF-1 transcriptional activity as well as interaction with chromatin remain elusive. We have recently shown that TFAP2A physically interacts with HIF-1 and hypoxia-dependent deSUMOylation of TFAP2A positively affects HIF-1 activity. We now present ChIP-seq analysis showing that TFAP2A resides together with HIF-1α on the promoters of a subset of hypoxia-regulated genes, the mRNA expression of which is downregulated by silencing of TFAP2A. Interestingly, CRISPR-mediated knockdown of TFAP2A expression under hypoxia decreased the occupancy of HIF-1α on these promoters and affected chromatin accessibility. Mechanistically, we reveal that the Ku70/Ku80 protein complex interacts with TFAP2A in a SUMO-dependent manner under hypoxia and participates in HIF-dependent gene expression. Moreover, using stable expression of TFAP2A forms that either lack or constitutively carry a SUMO modification, we could show that SUMOylation affects binding of TFAP2A to chromatin. Overall, our data suggest that TFAP2A is an important co-regulator of the HIF-1-dependent transcriptional response to hypoxia and SUMOylation fine-tunes this regulation. As both TFAP2A and HIF-1 play critical roles in cancer progression, a detailed characterization of their crosstalk could lead to novel therapeutic strategies for targeting and killing cancer cells in hypoxic tumors.
2025-05-23 | PXD053747 | Pride
Project description:Nucleolus-associated DNA was isolated from MEF cells before and after conditional knock-out of UBF and hybridized against genomic DNA in biological replicates. Two different types of immortalized MEF cells were used. MEFs were immortalized by genetic depletion of p53, iMEFs were immortalized by transfection of the SV40 Tt antigen.
2018-02-02 | GSE80441 | GEO
Project description:BackgroundCopy number variation is an important dimension of genetic diversity and has implications in development and disease. As an important model organism, the mouse is a prime candidate for copy number variant (CNV) characterization, but this has yet to be completed for a large sample size. Here we report CNV analysis of publicly available, high-density microarray data files for 351 mouse tail samples, including 290 mice that had not been characterized for CNVs previously.ResultsWe found 9634 putative autosomal CNVs across the samples affecting 6.87% of the mouse reference genome. We find significant differences in the degree of CNV uniqueness (single sample occurrence) and the nature of CNV-gene overlap between wild-caught mice and classical laboratory strains. CNV-gene overlap was associated with lipid metabolism, pheromone response and olfaction compared to immunity, carbohydrate metabolism and amino-acid metabolism for wild-caught mice and classical laboratory strains, respectively. Using two subspecies of wild-caught Mus musculus, we identified putative CNVs unique to those subspecies and show this diversity is better captured by wild-derived laboratory strains than by the classical laboratory strains. A total of 9 genic copy number variable regions (CNVRs) were selected for experimental confirmation by droplet digital PCR (ddPCR).ConclusionThe analysis we present is a comprehensive, genome-wide analysis of CNVs in Mus musculus, which increases the number of known variants in the species and will accelerate the identification of novel variants in future studies.
| S-EPMC4490682 | biostudies-literature