Unknown,Transcriptomics,Genomics,Proteomics

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Deep sequencing and functional annotation reveal miRNAs implicated in the cell senescence phenotype

ABSTRACT: In cell senescence, cultured cells cease proliferating and acquire aberrant gene expression patterns. MicroRNAs (miRNAs) modulate gene expression through translational repression or mRNA degradation, and have been implicated in senescence. We have used deep sequencing to carry out a comprehensive survey of miRNA expression and its involvement in cell senescence. Informatic analysis of small RNA sequence datasets from young and senescent IMR90 human fibroblasts identifies many known miRNAs, and a small number of novel miRNAs, that are regulated (either up or down) with cell senescence. Comparison with mRNA expression profiles revealed potential mRNA targets of the senescence-regulated miRNAs. The target mRNAs are enriched for genes involved in biological processes associated with cell senescence. This result greatly extends existing information on the role of miRNAs in cell senescence, and is consistent with miRNAs having a causal role in the process. Comprehensive survey of miRNA from young and senescent IMR90 fibroblasts using deep sequencing

ORGANISM(S): Homo sapiens

SUBMITTER: Dario Boffelli

PROVIDER: E-GEOD-27404 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Deep sequencing reveals novel microRNAs and regulation of microRNA expression during cell senescence.

Dhahbi Joseph M JM Atamna Hani H Boffelli Dario D Magis Wendy W Spindler Stephen R SR Martin David I K DI

PloS one 20110526 5

In cell senescence, cultured cells cease proliferating and acquire aberrant gene expression patterns. MicroRNAs (miRNAs) modulate gene expression through translational repression or mRNA degradation and have been implicated in senescence. We used deep sequencing to carry out a comprehensive survey of miRNA expression and involvement in cell senescence. Informatic analysis of small RNA sequence datasets from young and senescent IMR90 human fibroblasts identifies many miRNAs that are regulated (ei ...[more]

PMID: 21637828

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Project description:The expansion of repressive epigenetic marks has been implicated in heterochromatin formation during embryonic development, but the general applicability of this mechanism is unclear. Here we show that nuclear rearrangement of repressive histone marks H3K9me3 and H3K27me3 into non-overlapping structural layers characterizes senescence-associated heterochromatic foci (SAHF) formation in human fibroblasts. However, the global landscape of these repressive marks remains unchanged upon SAHF formation, suggesting that in somatic cells heterochromatin can be formed through the spatial repositioning of pre-existing repressively marked histones. This model is reinforced by the correlation of pre-senescent replication timing with both the subsequent layered structure of SAHFs and the global landscape of the repressive marks, allowing us to integrate microscopic and genomic information. Furthermore, modulation of SAHF structure does not affect the occupancy of these repressive marks nor vice versa. These experiments reveal that high-order heterochromatin formation and epigenetic remodeling of the genome can be discrete events. ChIP-seq for different histone marks in both growing and Ras-induced senescent fibroblasts, in the presence or absence of certain sh-RNAs K9me3Grow2.bed (growing) Chip Seq Analysis of H3K9me3 in ER:Ras expressing IMR90 human diploid fibroblasts d6 4OHT K9me3Sen2.bed (senescent) Chip Seq Analysis of H3K9me3 in ER:Ras expressing IMR90 human diploid fibroblasts with no treatment K9me2Grow3.bed (growing) Chip Seq Analysis of H3K9me2 in ER:Ras expressing IMR90 human diploid fibroblasts with no treatment K9me2Sen3.bed (senescent) Chip Seq Analysis of H3K9me2 in ER:Ras expressing IMR90 human diploid fibroblasts d6 4OHT K27me3Sen3.bed (senescent) Chip Seq Analysis of H3K27me3 in ER:Ras expressing IMR90 human diploid fibroblasts d6 4OHT K27me3Grow2.bed (growing) Chip Seq Analysis of H3K27me3 in ER:Ras expressing IMR90 human diploid fibroblasts with no treatment K36me3Grow2.bed (growing) Chip Seq Analysis of H3K36me3 in ER:Ras expressing IMR90 human diploid fibroblasts with no treatment K36me3Sen2.bed (senescent) Chip Seq Analysis of H3K36me3 in ER:Ras expressing IMR90 human diploid fibroblasts d6 4OHT K4me3Grow2.bed (growing) Chip Seq Analysis of H3K4me3 in ER:Ras expressing IMR90 human diploid fibroblasts with no treatment K4me3Sen3.bed (senescent) Chip Seq Analysis of H3K4me3 in ER:Ras expressing IMR90 human diploid fibroblasts d6 4OHT

Dataset Information

Deep sequencing and functional annotation reveal miRNAs implicated in the cell senescence phenotype

Publications

Deep sequencing reveals novel microRNAs and regulation of microRNA expression during cell senescence.

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