Profiling of chromatin accessibility and identification of general cis-regulatory mechanisms that control two ocular lens differentiation pathways
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ABSTRACT:
PROVIDER: PRJNA512208 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR8380080_1.fastq.gz | Fastqsanger.gz | |||
| SRR8380080_2.fastq.gz | Fastqsanger.gz | |||
| SRR8380081_1.fastq.gz | Fastqsanger.gz | |||
| SRR8380081_2.fastq.gz | Fastqsanger.gz | |||
| SRR8380074_1.fastq.gz | Fastqsanger.gz |
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Project description:We performed ATAC-seq for microdissected lens epithelium and fiber from E14.5 and P0.5 mouse lenses.Through investigating dynamics of chromatin changes during mouse lens fiber and epithelium differentiation, we identified spatial-temporal differential accessible regions and the enriched known and novel motifs. We also discovered some novel and known enhancers for the transcription factors and structural genes that are important in lens development. Additionally, a cross examination of Pax6 ChIP-seq with ATAC-seq data revealed novel Pax6 binding mechanisms.
2019-05-13 | GSE124497 | GEO
Project description:Identification of genes involved in ocular birth defects remains a challenge. To facilitate the identification of genes associated with cataract, we developed iSyTE (integrated Systems Tool for Eye gene discovery; http://bioinformatics.udel.edu/Research/iSyTE). iSyTE contains microarray gene expression profiles of the mouse embryonic lens as it transitions from the stage of placode invagination to that of vesicle formation. We identified differentially regulated genes by comparing lens microarray profiles to those representing whole embryonic body (WB) without ocular tissue. These were then utilized to generate a ranked list of lens-genes enrichment, which can be viewed as iSyTE tracks in the UCSC Genome browser to aid identification of genes with lens function. We microdissected embryonic lens from mice at E10.5, E11.5, and E12.5 (triplicate at each time point). To have a proper control, we also generated gene expression profiles of whole embryonic body (WB) at these time points. For comparative analysis, we also generated gene expression profiles of E13.5 tooth germs tissues, and matched WB. These profiles are used to identify lens and tooth specific gene expression enrichment at these embryonic time points. This dataset is then used to prioritize analysis of candidate cataract associated genes.
2012-02-16 | E-GEOD-32334 | biostudies-arrayexpress
Project description:Identification of genes involved in ocular birth defects remains a challenge. To facilitate the identification of genes associated with cataract, we developed iSyTE (integrated Systems Tool for Eye gene discovery; http://bioinformatics.udel.edu/Research/iSyTE). iSyTE contains microarray gene expression profiles of the mouse embryonic lens as it transitions from the stage of placode invagination to that of vesicle formation. We identified differentially regulated genes by comparing lens microarray profiles to those representing whole embryonic body (WB) without ocular tissue. These were then utilized to generate a ranked list of lens-genes enrichment, which can be viewed as iSyTE tracks in the UCSC Genome browser to aid identification of genes with lens function.
2012-02-16 | GSE32334 | GEO
Project description:Notch signaling is essential for proper lens development, however the specific requirements of individual Notch receptors has not been previously investigated. Here we report the lens phenotypes of Notch2 conditionally mutant mice, which exhibited severe microphthalmia, reduced pupillary openings, disrupted fiber cell morphology, eventual loss of the anterior epithelium, fiber cell dysgenesis, and cataracts. Notch2 mutants also had a persistent lens stalk phenotype at E11.5, and aberrant DNA synthesis in the fiber cell compartment by E14.5. Gene expression analyses showed elevated levels of the cell cycle regulators Cdkn1a (p21Cip1), Ccnd2 (CyclinD2) and Trp63 (p63) that negatively regulates Wnt signaling. Although removal of Notch2 phenocopied the increased proportion of fiber cells of Rbpj and Jag1 conditional mutant lenses, Notch2 is not required for AEL proliferation, suggesting that a different receptor regulates this process. Instead, we found that the Notch2 normally blocks progenitor cell death. Overall, we conclude that Notch2-mediated signaling regulates lens morphogenesis, apoptosis, cell cycle withdrawal, and secondary fiber cell differentiation. We have compared gene expression of ocular lenses of mice that are lens specific conditional mutants of Notch2 gene to that of littermate controls that had no ablation of Notch2 gene in the lens. Two lenses of each of the three conditional mutants and controls were pooled together and total RNA was harvested from embryonic day 19.5 (E19.5) lenses. Gene expression changes caused by absence of Notch2 gene in the lens were analyzed.
2011-12-31 | E-GEOD-31643 | biostudies-arrayexpress
Project description:We observed that the deletion of Anp32b led to severe defects in ocular development, such as anophthalmia and microphthalmia. Moreover, Anp32b was highly expressed in the lens, and Anp32b−/− embryos with microphthalmia typically exhibited severely impaired lens development. Mechanistically, ANP32B directly interacted with paired box protein 6 (PAX6), a master transcriptional regulator of ocular development, and enhanced its transcriptional activity. In line with these findings, overexpression of PAX6 partially but significantly reversed the inhibition of proliferation observed in ANP32B knockdown cells. Collectively, our findings reveal that ANP32B-deficiency suppresses ocular development by repression of PAX6 and identify ANP32B as a viable therapeutic target for ocular developmental defects.
2025-06-02 | GSE269101 | GEO
Project description:Purpose: Transcriptome is the entire repertoire of all transcripts present in a cell at any particular time. We undertook next-generation whole transcriptome sequencing approach to gain insight of the transcriptional landscape of the developing mouse lens. Methods: We ascertained mice lenses at six developmental time points including two embryonic (E15 and E18) and four postnatal stages (P0, P3, P6, and P9). The ocular tissue at each time point was maintained as two distinct pools serving as biological replicates for each developmental stage. The mRNA and small RNA libraries were paired-end sequenced on Illumina HiSeq 2000 and subsequently analyzed using bioinformatics tools. Results: Mapping of mRNA and small RNA libraries generated 187.56 and 154.22 million paired-end reads, respectively. We detected a total of 14,465 genes in the mouse ocular lens. Of these, 46 genes exhibited 40-fold differential expression compared to transcriptional levels at E15. Likewise, small RNA profiling identified 379 microRNAs (miRNAs) expressed in mouse lens. Of these, 49 miRNAs manifested an 8-fold or higher differential expression when compared, as above to the microRNA expression at E15. Conclusion: We report the first comprehensive profile of developing murine lens transcriptome including both mRNA and miRNA through next-generation RNA sequencing. A complete repository of the lens transcriptome of six developmental time points will be monumental in elucidating processes essential for development of the ocular lens and maintenance its transparency. Whole transcrtiome and microRNA profilling of mouse lens using 2 embryonic (E15 and E18) and 4 postnatal stages (P0, P3, P6 and P9) in duplicates through high-throughput sequening using Illumina HiSeq2000.
2015-10-29 | E-GEOD-69221 | biostudies-arrayexpress
Project description:BackgroundPromoters and enhancers are cis-regulatory DNA sequences that control specificity and quantity of transcription. Both are rich on clusters of cis-acting sites that interact with sequence-specific DNA-binding transcription factors (TFs). At the level of chromatin, these regions display increased nuclease sensitivity, reduced nucleosome density, including nucleosome-free regions, and specific combinations of posttranslational modifications of core histone proteins. Together, "open" and "closed" chromatins represent transcriptionally active and repressed states of individual genes, respectively. Cellular differentiation is marked by changes in local chromatin structure. Lens morphogenesis, regulated by TF Pax6, includes differentiation of epithelial precursor cells into lens fibers in parallel with differentiation of epithelial precursors into the mature lens epithelium.ResultsUsing ATAC-seq, we investigated dynamics of chromatin changes during mouse lens fibers and epithelium differentiation. Tissue-specific features of these processes are demonstrated via comparative studies of embryonic stem cells, forebrain, and liver chromatins. Unbiased analysis reveals cis-regulatory logic of lens differentiation through known (e.g., AP-1, Ets, Hsf4, Maf, and Pax6 sites) and novel (e.g., CTCF, Tead, and NF1) motifs. Twenty-six DNA-binding TFs, recognizing these cis-motifs, are markedly up-regulated in differentiating lens fibers. As specific examples, our ATAC-seq data uncovered both the regulatory regions and TF binding motifs in Foxe3, Prox1, and Mip loci that are consistent with previous, though incomplete, experimental data. A cross-examination of Pax6 binding with ATAC-seq data demonstrated that Pax6 bound to both open (H3K27ac and P300-enriched) and closed chromatin domains in lens and forebrain.ConclusionsOur study has generated the first lens chromatin accessibility maps that support a general model of stage-specific chromatin changes associated with transcriptional activities of batteries of genes required for lens fiber cell formation. Analysis of active (or open) promoters and enhancers reveals important cis-DNA motifs that establish the molecular foundation for temporally and spatially regulated gene expression in lens. Together, our data and models open new avenues for the field to conduct mechanistic studies of transcriptional control regions, reconstruction of gene regulatory networks that govern lens morphogenesis, and identification of cataract-causing mutations in noncoding sequences.
| S-EPMC6498704 | biostudies-literature
Project description:The vertebrate ocular lens consists of two basic cell types: the lens fibers, highly specialized cells that make up the bulk of the lens and are the basis for its unique optical characteristics, and the epithelial cells that cover the anterior hemisphere and acts as a stem cell population for progenitors of new fibers. The forkhead transcription factor FoxE3 is essential for maintenance, proliferation and survival of the epithelial cells, and silencing of the FoxE3 gene coincides with the cell cycle arrest that marks initiation of fiber cell differentiation. Here we have used transgenic ectopic expression of murine Foxe3 in fiber cells to investigate the consequences of persistent Foxe3 expression during fiber differentiation. Microarray transcript profiling showed that ectopic Foxe3 caused a general increase in mRNAs which are normally enriched in epithelial cells, consistent with an epithelialization of the transgenic fibers. Experiment Overall Design: Whole lenses from P2 animals were dissected and genotyped. 12 lenses from each genotype were used for RNA extraction and hybridization to Affymetrix arrays. Total of 3 replicates/genotype.
2008-10-20 | E-GEOD-9711 | biostudies-arrayexpress
Project description:Purpose: Transcriptome is the entire repertoire of all transcripts present in a cell at any particular time. We undertook next-generation whole transcriptome sequencing approach to gain insight of the transcriptional landscape of the developing mouse lens. Methods: We ascertained mice lenses at six developmental time points including two embryonic (E15 and E18) and four postnatal stages (P0, P3, P6, and P9). The ocular tissue at each time point was maintained as two distinct pools serving as biological replicates for each developmental stage. The mRNA and small RNA libraries were paired-end sequenced on Illumina HiSeq 2000 and subsequently analyzed using bioinformatics tools. Results: Mapping of mRNA and small RNA libraries generated 187.56 and 154.22 million paired-end reads, respectively. We detected a total of 14,465 genes in the mouse ocular lens. Of these, 46 genes exhibited 40-fold differential expression compared to transcriptional levels at E15. Likewise, small RNA profiling identified 379 microRNAs (miRNAs) expressed in mouse lens. Of these, 49 miRNAs manifested an 8-fold or higher differential expression when compared, as above to the microRNA expression at E15. Conclusion: We report the first comprehensive profile of developing murine lens transcriptome including both mRNA and miRNA through next-generation RNA sequencing. A complete repository of the lens transcriptome of six developmental time points will be monumental in elucidating processes essential for development of the ocular lens and maintenance its transparency.
2015-10-29 | GSE69221 | GEO
Project description:Notch signaling is essential for proper lens development, however the specific requirements of individual Notch receptors has not been previously investigated. Here we report the lens phenotypes of Notch2 conditionally mutant mice, which exhibited severe microphthalmia, reduced pupillary openings, disrupted fiber cell morphology, eventual loss of the anterior epithelium, fiber cell dysgenesis, and cataracts. Notch2 mutants also had a persistent lens stalk phenotype at E11.5, and aberrant DNA synthesis in the fiber cell compartment by E14.5. Gene expression analyses showed elevated levels of the cell cycle regulators Cdkn1a (p21Cip1), Ccnd2 (CyclinD2) and Trp63 (p63) that negatively regulates Wnt signaling. Although removal of Notch2 phenocopied the increased proportion of fiber cells of Rbpj and Jag1 conditional mutant lenses, Notch2 is not required for AEL proliferation, suggesting that a different receptor regulates this process. Instead, we found that the Notch2 normally blocks progenitor cell death. Overall, we conclude that Notch2-mediated signaling regulates lens morphogenesis, apoptosis, cell cycle withdrawal, and secondary fiber cell differentiation.
2011-12-31 | GSE31643 | GEO