Epigenetic regulation of cell type-specific expression patterns in the human mammary epithelium
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: PRJNA142401PRJNA142405PRJNA142403PRJNA135389
ORGANISM(S): Homo sapiens
PROVIDER: GSE26141 | GEO | 2011/03/01
SECONDARY ACCESSION(S): PRJNA135389
REPOSITORIES: GEO
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Project description:Differentiation is an epigenetic program that involves the gradual loss of pluripotency and acquisition of cell type-specific features. Understanding these processes requires genome-wide analysis of epigenetic and gene expression profiles, which have been challenging in primary tissue samples due to limited numbers of cells available. Here we describe the application of high-throughput sequencing technology for profiling histone and DNA methylation, as well as gene expression patterns of normal human mammary progenitor-enriched and luminal lineage-committed cells. We observed significant differences in histone H3 lysine 27 tri-methylation (H3K27me3) enrichment and DNA methylation of genes expressed in a cell type-specific manner, suggesting their regulation by epigenetic mechanisms and a dynamic interplay between the two processes that together define developmental potential. The technologies we developed and the epigenetically regulated genes we identified will accelerate the characterization of primary cell epigenomes and the dissection of human mammary epithelial lineage-commitment and luminal differentiation.
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Project description:Here we describe the application of high-throughput sequencing technology for profiling histone and DNA methylation, and gene expression patterns of normal human mammary progenitor-enriched and luminal lineage-committed cells. We observed significant differences in histone H3 lysine 27 tri-methylation (H3K27me3) enrichment and DNA methylation of genes expressed in a cell type-specific manner, suggesting their regulation by epigenetic mechanisms and a dynamic interplay between the two processes that together define developmental potential. The technologies we developed and the epigenetically regulated genes we identified will accelerate the characterization of primary cell epigenomes and the dissection of human mammary epithelial lineage-commitment and luminal differentiation.
2011-03-01 | GSE26139 | GEO
Project description:Here we describe the application of high-throughput sequencing technology for profiling histone and DNA methylation, and gene expression patterns of normal human mammary progenitor-enriched and luminal lineage-committed cells. We observed significant differences in histone H3 lysine 27 tri-methylation (H3K27me3) enrichment and DNA methylation of genes expressed in a cell type-specific manner, suggesting their regulation by epigenetic mechanisms and a dynamic interplay between the two processes that together define developmental potential. The technologies we developed and the epigenetically regulated genes we identified will accelerate the characterization of primary cell epigenomes and the dissection of human mammary epithelial lineage-commitment and luminal differentiation. Global profiling of differentially methylated regions in 2 cell types from 6 individuals.
2011-03-01 | E-GEOD-26139 | biostudies-arrayexpress
Project description:Here we describe the application of high-throughput sequencing technology for profiling histone and DNA methylation, and gene expression patterns of normal human mammary progenitor-enriched and luminal lineage-committed cells. We observed significant differences in histone H3 lysine 27 tri-methylation (H3K27me3) enrichment and DNA methylation of genes expressed in a cell type-specific manner, suggesting their regulation by epigenetic mechanisms and a dynamic interplay between the two processes that together define developmental potential. The technologies we developed and the epigenetically regulated genes we identified will accelerate the characterization of primary cell epigenomes and the dissection of human mammary epithelial lineage-commitment and luminal differentiation. Global transcriptome profilings of 15 samples in normal breast tissue using Sage-Seq.
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Project description:Here we describe the application of high-throughput sequencing technology for profiling histone and DNA methylation, and gene expression patterns of normal human mammary progenitor-enriched and luminal lineage-committed cells. We observed significant differences in histone H3 lysine 27 tri-methylation (H3K27me3) enrichment and DNA methylation of genes expressed in a cell type-specific manner, suggesting their regulation by epigenetic mechanisms and a dynamic interplay between the two processes that together define developmental potential. The technologies we developed and the epigenetically regulated genes we identified will accelerate the characterization of primary cell epigenomes and the dissection of human mammary epithelial lineage-commitment and luminal differentiation. Examination of histone H3K27me3 modifications in 2 cell types from 3 individuals and H3K4me3 modifications in 2 cell types from one individual sample.
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Project description:Here we describe the application of high-throughput sequencing technology for profiling histone and DNA methylation, and gene expression patterns of normal human mammary progenitor-enriched and luminal lineage-committed cells. We observed significant differences in histone H3 lysine 27 tri-methylation (H3K27me3) enrichment and DNA methylation of genes expressed in a cell type-specific manner, suggesting their regulation by epigenetic mechanisms and a dynamic interplay between the two processes that together define developmental potential. The technologies we developed and the epigenetically regulated genes we identified will accelerate the characterization of primary cell epigenomes and the dissection of human mammary epithelial lineage-commitment and luminal differentiation.
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Project description:Here we describe the application of high-throughput sequencing technology for profiling histone and DNA methylation, and gene expression patterns of normal human mammary progenitor-enriched and luminal lineage-committed cells. We observed significant differences in histone H3 lysine 27 tri-methylation (H3K27me3) enrichment and DNA methylation of genes expressed in a cell type-specific manner, suggesting their regulation by epigenetic mechanisms and a dynamic interplay between the two processes that together define developmental potential. The technologies we developed and the epigenetically regulated genes we identified will accelerate the characterization of primary cell epigenomes and the dissection of human mammary epithelial lineage-commitment and luminal differentiation.
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Project description:Epigenetic mechanisms are important regulators of cell type-specific genes, including miRNAs. In order to identify cell type-specific miRNAs regulated by epigenetic mechanisms, we undertook a global analysis of miRNA expression and epigenetic states in three isogenic pairs of human mammary epithelial cells (HMEC) and human mammary fibroblasts (HMF), which represent two differentiated cell types typically present within a given organ, each with a distinct phenotype and a distinct epigenotype. While miRNA expression and epigenetic states showed strong interindividual concordance within a given cell type, almost 10% of the expressed miRNA showed a cell type-specific pattern of expression that was linked to the epigenetic state of their promoter. The tissue-specific miRNA genes were epigenetically repressed in nonexpressing cells by DNA methylation (38%) and H3K27me3 (58%), with only a small set of miRNAs (21%) showing a dual epigenetic repression where both DNA methylation and H3K27me3 were present at their promoters, such as MIR10A and MIR10B. Individual miRNA clusters of closely related miRNA gene families can each display cell type-specific repression by the same or complementary epigenetic mechanisms, such as the MIR200 family, and MIR205, where fibroblasts repress MIR200C/141 by DNA methylation, MIR200A/200B/429 by H3K27me3, and MIR205 by both DNA methylation and H3K27me3. Since deregulation of many of the epigenetically regulated miRNAs that we identified have been linked to disease processes such as cancer, it is predicted that compromise of the epigenetic control mechanisms is important for this process. Overall, these results highlight the importance of epigenetic regulation in the control of normal cell type-specific miRNA expression.
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Project description:Epigenetic machinery contributes to gene regulation in eukaryotic species. However, the machinery including more than 600 epigenetic regulator (ER) genes responsible for reading, writing, and erasing histone modifications and DNA modifications remains largely uncharacterized across species. We compile a comprehensive list of ERs based on an evolutionary analysis across 23 species, which is the most comprehensive ER list in various species until recently. We further perform comparative transcriptomic analyses across different tissues in humans, mice, as well as other amniote species. We observe a consistent tissue-of-origin expression specificity pattern of duplicated ER genes across species and suggest links between expression specificity and ER gene evolution as well as ER function. Additional analyses further suggest that ER duplication can generate tissue-specific ER genes with the same epigenetic substrates, which may be closely related to their regulatory specificity in tissue development. Our work can serve as a foundation to better comprehend the tissue-specific expression patterns of ER genes from an evolutionary perspective and also the functional implications of ERs in tissue-specific epigenetic regulation.
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