Unknown,Transcriptomics,Genomics,Proteomics

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Temporal changes of gene expression in mouse heart, kidney and lung during juvenile growth

ABSTRACT: Temporal changes of gene expression from 1-wk- to 4-wk and 8-wk-old mouse in heart, kidney and lung. Mammalian somatic growth is rapid in early postnatal life but then slows and eventually ceases in multiple tissues. We hypothesized that there exists a postnatal gene expression program that is common to multiple tissues and is responsible for this coordinate growth deceleration. Consistent with this hypothesis, microarray analysis identified >1600 genes that were regulated with age coordinately in kidney, lung, and heart of juvenile mice, including many genes that regulate proliferation. As examples, we focused on three growth-promoting genes, Igf2, Mest, and Peg3, that were markedly downregulated with age. We conclude that there exists an extensive genetic program occurring during postnatal life. Many of the involved genes are regulated coordinately in multiple organs, including many genes that regulate cell proliferation. At least some of these are themselves apparently regulated by growth, suggesting that, in the embryo, a gene expression pattern is established that allows for rapid somatic growth of multiple tissues but then, during postnatal life, this growth leads to negative-feedback changes in gene expression that in turn slow and eventually halt somatic growth, thus imposing a fundamental limit on adult body size. To compare gene expression between fast-growing animals and more slowly growing animals, we extracted total mRNA from kidney and lung in 1-wk, 4-wk, and 8-wk-old mice (5 animals each).

ORGANISM(S): Mus musculus

SUBMITTER: Julian Lui

PROVIDER: E-GEOD-38754 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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An extensive genetic program occurring during postnatal growth in multiple tissues.

Finkielstain Gabriela P GP Forcinito Patricia P Lui Julian C K JC Barnes Kevin M KM Marino Rose R Makaroun Sami S Nguyen Vina V Lazarus Jacob E JE Nilsson Ola O Baron Jeffrey J

Endocrinology 20081126 4

Mammalian somatic growth is rapid in early postnatal life but then slows and eventually ceases in multiple tissues. We hypothesized that there exists a postnatal gene expression program that is common to multiple tissues and is responsible for this coordinate growth deceleration. Consistent with this hypothesis, microarray analysis identified more than 1600 genes that were regulated with age (1 vs. 4 wk) coordinately in kidney, lung, and heart of male mice, including many genes that regulate pro ...[more]

PMID: 19036884

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Project description:During early postnatal life, extensive changes in gene expression occur concomitantly in multiple major organs, indicating the existence of a common core developmental genetic program. This program includes hundreds of growth-promoting genes that are downregulated with age in liver, kidney, lung, and heart, and there is evidence that this component of the program drives the widespread decline in cell proliferation that occurs in juvenile life, as organs approach adult sizes. To investigate epigenetic changes that might orchestrate this program, we performed chromatin immunoprecipitation-promoter tiling array to assess temporal changes in histone H3K4 and H3K27 trimethylation (me3) at promoter regions throughout the genome in kidney and lung, comparing 1- to 4-wk-old mice. We found extensive genome-wide shifts in H3K4me3 and H3K27me3 occurring with age in both kidney and lung. The number of genes with concordant changes in the two organs was far greater than expected by chance. Temporal changes in H3K4me3 showed a strong, positive association with changes in gene expression, assessed by microarray, whereas changes in H3K27me3 showed a negative association. Gene ontology analysis indicated that shifts in specific histone methylation marks were associated with specific developmental functions. Of particular interest, genes with decreases in H3K4me3 with age in both organs were strongly implicated in cell cycle and cell proliferation functions. Taken together, the findings suggest that the common core developmental program of gene expression which occurs in multiple organs during juvenile life is associated with a common core developmental program of histone methylation. In particular, declining H3K4me3 is strongly associated with gene downregulation and occurs in the promoter regions of many growth-regulating genes, suggesting that this change in histone methylation may contribute to the component of the genetic program that drives juvenile body growth deceleration. Tissues samples were collect from Lung (1 and 4 week old) and Kindey (1 and 4 week old) respectively with four biological replications of mice that were collected, frozen in liquid nitrogen, and stored at -70 °C

Dataset Information

Temporal changes of gene expression in mouse heart, kidney and lung during juvenile growth

Publications

An extensive genetic program occurring during postnatal growth in multiple tissues.

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