Unknown,Transcriptomics,Genomics,Proteomics

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Random monoallelic expression in the mouse: SNP array data

ABSTRACT: Random monoallelic expression is defined by the allele-specific expression of genes, and by the fact that for an individual cell this monoallelic expression is neither obligate nor necessarily coordinated with the allelic expression in other cells. In order to find novel examples of random monoallelic expression in mouse, we did a transcriptome-wide survey of allele-specific gene expression in two different immortalized cell types. Lymphoblast cell lines and fibroblast cell lines were established (both clonal and nonclonal) and were used as a source of both nuclear RNA and genomic DNA. These samples were assessed for allele-specific gene expression using a custom-designed Mouse SNP Chip. A large number of genes (over 10% of those that were assessed in lymphoblast clones) displayed random monoallelic expression. For each cell line, two replicate samples of ds-cDNA were assessed for monoallelic expression, while genomic DNA was assessed as a control for possible LOH events. Nonclonal samples were used as controls for cis-acting allelic bias.

ORGANISM(S): Mus musculus

SUBMITTER: Alexander Gimelbrant

PROVIDER: E-GEOD-35678 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Autosomal monoallelic expression in the mouse.

Zwemer Lillian M LM Zak Alexander A Thompson Benjamin R BR Kirby Andrew A Daly Mark J MJ Chess Andrew A Gimelbrant Alexander A AA

Genome biology 20120220 2

<h4>Background</h4>Random monoallelic expression defines an unusual class of genes displaying random choice for expression between the maternal and paternal alleles. Once established, the allele-specific expression pattern is stably maintained and mitotically inherited. Examples of random monoallelic genes include those found on the X-chromosome and a subset of autosomal genes, which have been most extensively studied in humans. Here, we report a genome-wide analysis of random monoallelic expres ...[more]

PMID: 22348269

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Project description:In diploid eukaryotic organisms, both alleles of each autosomal gene are usually assumed to be simultaneously expressed at similar levels. However, some genes can be expressed preferentially or strictly from a single allele, a process known as monoallelic expression. Classic monoallelic expression of X-chromosome-linked genes, olfactory receptor genes and developmentally imprinted genes is the result of epigenetic modifications. Genetic-origin-dependent monoallelic expression, however, is caused by cis-regulatory differences between the alleles. There is a paucity of systematic study to investigate these phenomena across multiple tissues, and the mechanisms underlying such monoallelic expression are not yet fully understood. Here we provide a detailed portrait of monoallelic gene expression across multiple tissues/cell lines in a hybrid mouse cross between the Mus musculus strain C57BL/6J and the Mus spretus strain SPRET/EiJ. We observed pervasive tissue-dependent allele-specific gene expression: in total, 1,839 genes exhibited monoallelic expression in at least one tissue, and 410 genes in at least two tissues. Among these 88 are monoallelic genes with different active alleles between tissues, probably representing genetic-origin-dependent monoallelic expression. We also identified six autosomal monoallelic genes with the active allele being identical in all eight tissues, which are likely novel candidates of imprinted genes. To depict the underlying regulatory mechanisms at the chromatin layer, we performed ATAC-seq in two different cell lines derived from the F1 mouse. Consistent with the global expression pattern, cell-type dependent monoallelic peaks were found, and a higher proportion of C57BL/6J-active peaks were observed in both cell types, implying possible species-specific regulation. Finally, only a small part of monoallelic gene expression could be explained by allelic differences in chromatin organization in promoter regions, suggesting that other distal elements may play important roles in shaping the patterns of allelic gene expression across tissues.

Dataset Information

Random monoallelic expression in the mouse: SNP array data

Publications

Autosomal monoallelic expression in the mouse.

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