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Genomic dissection of conserved transcriptional regulation in intestinal epithelial cells [human]

ABSTRACT: We profiled genome-wide accesssible chromatin data and RNA-seq from four species (zebrafish, stickleback, mouse, and human) to identify commonly regulated genes and regulatory metods in intestinal epithelial cells (IECs). We identify a group genes that are commonly expressed in IECs and genes that are commonly expressed along the length of the intestine in fish and mammals. Using accessible chromatin data we identified enriched transcription factor binding site motifs In IECs and sites that are commonly accessible in IECs in all species. Finally, we confirm the ability for these regions from multiple species to drive conserved expression in IECs using a zebrafish reporter assay.

ORGANISM(S): Homo sapiens

PROVIDER: GSE94935 | GEO | 2017/05/02

SECONDARY ACCESSION(S): PRJNA374871

REPOSITORIES: GEO

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Genomic dissection of conserved transcriptional regulation in intestinal epithelial cells [Stickleback]

Project description:We profiled genome-wide accesssible chromatin data and RNA-seq from four species (zebrafish, stickleback, mouse, and human) to identify commonly regulated genes and regulatory metods in intestinal epithelial cells (IECs). We identify a group genes that are commonly expressed in IECs and genes that are commonly expressed along the length of the intestine in fish and mammals. Using accessible chromatin data we identified enriched transcription factor binding site motifs In IECs and sites that are commonly accessible in IECs in all species. Finally, we confirm the ability for these regions from multiple species to drive conserved expression in IECs using a zebrafish reporter assay.

2017-05-02 | GSE94934 | GEO

Genomic dissection of conserved transcriptional regulation in intestinal epithelial cells [zebrafish]

2017-05-02 | GSE94933 | GEO

Microbiota modulate transcription in the intestinal epithelium without remodeling the accessible chromatin landscape

Project description:We profiled transcriptome and accessible chromatin landscapes in intestinal epithelial cells (IECs) from mice reared in the presence or absence of microbiota. We show that regional differences in gene transcription along the intestinal tract were accompanied by major alterations in chromatin organization. Surprisingly, we discovered that microbiota modify host gene transcription in IECs without significantly impacting the accessible chromatin landscape. Instead, microbiota regulation of host gene transcription might be achieved by differential expression of specific TFs and enrichment of their binding sites in nucleosome depleted CRRs near target genes. Our results suggest that the chromatin landscape in IECs is pre-programmed by the host in a region-specific manner to permit responses to microbiota through binding of open CRRs by specific TFs. mRNA and accessible chromatin (DNase-seq) profiles from colonic and ileal IECs were compared between conventionally-raised (CR), germ-free (GF), and conventionalized (CV) C57BL/6 mice.

2014-06-07 | E-GEOD-57919 | biostudies-arrayexpress

Conserved pleiotropy of an ancient plant homeobox gene uncovered by cis-regulatory dissection

Project description:Divergence of gene function is a hallmark of evolution, but assessing functional divergence over deep time is not trivial. The few alleles available for cross-species studies often fail to expose the entire functional spectrum of genes, potentially obscuring deeply conserved pleiotropic roles. Here, we explore the functional divergence of WUSCHEL HOMEOBOX9 (WOX9), suggested to have species-specific roles in embryo and inflorescence development. Using a cis-regulatory editing drive system, we generated a comprehensive allelic series in tomato, which revealed hidden pleiotropic roles for WOX9. Analysis of accessible chromatin and conserved cis-regulatory sequences identified the regions responsible for this pleiotropic activity, the functions of which were conserved in groundcherry, a tomato relative. Mimicking these alleles in arabidopsis, distantly related to tomato and groundcherry, revealed new inflorescence phenotypes, exposing a deeply conserved pleiotropy. We suggest that targeted cis-regulatory mutations can uncover conserved gene functions and reduce undesirable effects in crop improvement.

2021-01-14 | GSE164297 | GEO

Microbiota modulate transcription in the intestinal epithelium without remodeling the accessible chromatin landscape

2014-06-07 | GSE57919 | GEO

Identification of DNA methylation-independent epigenetic events underlying clear cell renal cell carcinoma

Project description:Alterations in chromatin accessibility independent of DNA methylation can affect cancer-related gene expression, but are often overlooked in conventional epigenomic profiling approaches. In this study, we describe a cost-effective and computationally simple assay called AcceSssIble to simultaneously interrogate DNA methylation and chromatin accessibility alterations in primary human clear cell renal cell carcinomas (ccRCC). Our study revealed significant perturbations to the ccRCC epigenome, and identified gene expression changes that were specifically attributed to the chromatin accessibility status whether or not DNA methylation was involved. Compared to commonly mutated genes in ccRCC, such as the von Hippel-Lindau (VHL) tumor suppressor, the genes identified by AcceSssIble comprised distinct pathways and more frequently underwent epigenetic changes, suggesting that genetic and epigenetic alterations could be independent events in ccRCC. Specifically, we found unique DNA methylation-independent promoter accessibility alterations in pathways mimicking VHL deficiency. Overall, this study provides a novel approach for identifying new epigenetic-based therapeutic targets, previously undetectable by DNA methylation studies alone, that may complement current genetic-based treatment strategies. Examination of 3 different histone modifications in 2 patient tumor and adjacent normal samples.

2016-03-15 | E-GEOD-75597 | biostudies-arrayexpress

Identification of DNA methylation-independent epigenetic events underlying clear cell renal cell carcinoma

2016-03-15 | GSE75597 | GEO

Single nuclei chromatin profiles of midbrain from genetically distinct mouse strains reveal cell identity transcription factors and cell type-specific gene regulatory variation

Project description:Here we report 20 658 single nuclei chromatin accessibility profiles of ventral midbrain cell types from two genetically diverse and commonly used mouse strains, C57BL6/J and A/J. In total we identify over 260 000 unique accessible sites. The distinct chromatin profiles are consistent with gene expression levels from single cell RNA-seq data and can distinguish ten midbrain cell types. Transcription factor (TF) binding motifs enriched at accessible regions controlling cell identity genes highlight the key TFs of each major cell type. The gene regulatory differences between the mouse strains manifest more on transcriptome than chromatin level.

2022-01-14 | E-MTAB-9225 | biostudies-arrayexpress

Proteomics support the threespine stickleback egg coat as a protective oocyte envelope

Project description:After the end of the last ice age, ancestrally marine threespine stickleback fish (Gasterosteus aculeatus) have undergone an adaptive radiation into freshwater environments throughout the Northern Hemisphere, creating an excellent model system for studying molecular adaptation and speciation. Stickleback populations are reproductively isolated to varying degrees, despite the fact that they can be crossed in the lab to produce viable offspring. Ecological and behavioral factors have been suggested to underlie incipient stickleback speciation. However, reproductive proteins represent a previously unexplored driver of speciation. As mediators of gamete recognition during fertilization, reproductive proteins both create and maintain species boundaries. Gamete recognition proteins are also frequently found to be rapidly evolving, and their divergence may culminate in reproductive isolation and ultimately speciation. As an initial investigation into the contribution of reproductive proteins to stickleback reproductive isolation, we characterized the egg coat proteome of threespine stickleback eggs. In agreement with other teleosts, we find that stickleback egg coats are comprised of homologs to the zona pellucida (ZP) proteins ZP1 and ZP3. We explore aspects of stickleback ZP protein biology, including glycosylation, disulfide bonding, and sites of synthesis, and find many substantial differences compared to their mammalian homologs. Furthermore, molecular evolutionary analyses indicate that ZP3, but not ZP1, has experienced positive Darwinian selection across teleost fish. Taken together, these changes to stickleback ZP protein architecture suggest that the egg coats of stickleback fish, and perhaps fish more generally, have evolved to fulfill a more protective functional role than their mammalian counterparts.

2021-05-26 | PXD017489 | Pride

Proteomics support the threespine stickleback egg coat as a protective oocyte envelope

2021-05-26 | PXD017488 | Pride

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