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Genome-wide Human Placenta Enhancer Identification and Association with Function, Differentiation, and Disease.

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE222035 | GEO | 2023/09/22

REPOSITORIES: GEO

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Genome-wide Human Placenta Enhancer Identification and Association with Function, Differentiation, and Disease [RNA-seq]

Project description:Placental gene expression changes associated with advancing gestational age in weeks or by trimester were identified by differential expression analysis

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Genome-wide Human Placenta Enhancer Identification and Association with Function, Differentiation, and Disease [PRO-seq]

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Genome-wide Human Placenta Enhancer Identification and Association with Function, Differentiation, and Disease [CHIP-seq]

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Genome-wide Human Placenta Enhancer Identification and Association with Function, Differentiation, and Disease.

Project description:Genome-wide Human Placenta Enhancer Identification and Association with Function, Differentiation, and Disease.

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Genome-wide Human Placenta Enhancer Identification and Association with Function, Differentiation, and Disease [CHIP-seq]

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Genome-wide Human Placenta Enhancer Identification and Association with Function, Differentiation, and Disease [PRO-seq]

Project description:Genome-wide Human Placenta Enhancer Identification and Association with Function, Differentiation, and Disease [PRO-seq]

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Genome-wide Human Placenta Enhancer Identification and Association with Function, Differentiation, and Disease [RNA-seq]

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Genome-wide identification of transcriptional enhancers During human placental development and association with function, differentiation, and disease.

Project description:The placenta is a dynamic organ which must perform a remarkable variety of functions during its relatively short existence in order to support a developing fetus. These functions include nutrient delivery, gas exchange, waste removal, hormone production, and immune barrier functions. Proper placenta development and function is critical for healthy pregnancy outcomes, but the underlying genomic regulatory events that control this process remain largely unknown. We hypothesized that mapping sites of transcriptional enhancer activity and associated changes in gene expression across gestation in human placenta tissue would identify genomic loci and predicted transcription factor activity related to critical placenta functions. We used a suite of genomic assays (i.e. RNA-seq, PRO-seq, ChIP-seq) and computational pipelines to identify a set of >20,000 enhancers which are active at various time points in gestation. Changes in the activity of these enhancers correlate with changes in gene expression. In addition, some of these enhancers encode risk for adverse pregnancy outcomes. We further show that integrating enhancer activity, transcription factor motif analysis, and transcription factor expression can identify distinct sets of transcription factors predicted to be more active either in early pregnancy or at term. Knockdown of selected identified transcription factors in a trophoblast stem cell culture model altered the expression of key placental marker genes. These observations provide a framework for future mechanistic studies of individual enhancer-transcription factor-target gene interactions and have the potential to inform genetic risk prediction for adverse pregnancy outcomes.

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Genome-wide identification of hypoxia-induced enhancer regions.

Project description:Here we present a genome-wide method for de novo identification of enhancer regions. This approach enables massively parallel empirical investigation of DNA sequences that mediate transcriptional activation and provides a platform for discovery of regulatory modules capable of driving context-specific gene expression. The method links fragmented genomic DNA to the transcription of randomer molecule identifiers and measures the functional enhancer activity of the library by massively parallel sequencing. We transfected a Drosophila melanogaster library into S2 cells in normoxia and hypoxia, and assayed 4,599,881 genomic DNA fragments in parallel. The locations of the enhancer regions strongly correlate with genes up-regulated after hypoxia and previously described enhancers. Novel enhancer regions were identified and integrated with RNAseq data and transcription factor motifs to describe the hypoxic response on a genome-wide basis as a complex regulatory network involving multiple stress-response pathways. This work provides a novel method for high-throughput assay of enhancer activity and the genome-scale identification of 31 hypoxia-activated enhancers in Drosophila.

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