Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Regulatory element copy number differences shape primate expression profiles.

ABSTRACT: Gene expression differences are shaped by selective pressures and contribute to phenotypic differences between species. We identified 964 copy number differences (CNDs) of conserved sequences across 3 primate species and examined their potential effects on gene expression profiles. Samples with copy number different genes had significantly different expression than samples with neutral copy number. Genes encoding regulatory molecules differed in copy number and were associated with significant expression differences. Additionally, we identified 127 CNDs which were processed pseudogenes and some of which were expressed. Furthermore, there were copy number different regulatory regions such as ultraconserved elements and long intergenic noncoding RNAs with the potential to affect expression. We postulate that CNDs of these conserved sequences fine-tune developmental pathways by altering the levels of RNA. Gene expression patterns were compared between human, chimpanzee and rhesus macaque lymphoblastoid cell lines using RNA-Seq. Samples from 6 individuals of each species were used. The 6 human samples were previously published as a part of GEO record GSE19480 (samples GSM485426, GSM485428, GSM485468, GSM485410, GSM485413 and GSM485414). The 6 chimpanzee and 6 rhesus macaquesamples are included in the current record (GSE38572).

ORGANISM(S): Pan troglodytes

SUBMITTER: Darren Cusanovich

PROVIDER: E-GEOD-38572 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Regulatory element copy number differences shape primate expression profiles.

Iskow Rebecca C RC Gokcumen Omer O Abyzov Alexej A Malukiewicz Joanna J Zhu Qihui Q Sukumar Ann T AT Pai Athma A AA Mills Ryan E RE Habegger Lukas L Cusanovich Darren A DA Rubel Meagan A MA Perry George H GH Gerstein Mark M Stone Anne C AC Gilad Yoav Y Lee Charles C

Proceedings of the National Academy of Sciences of the United States of America 20120713 31

Gene expression differences are shaped by selective pressures and contribute to phenotypic differences between species. We identified 964 copy number differences (CNDs) of conserved sequences across three primate species and examined their potential effects on gene expression profiles. Samples with copy number different genes had significantly different expression than samples with neutral copy number. Genes encoding regulatory molecules differed in copy number and were associated with significa ...[more]

PMID: 22797897

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Project description:Human embryonic stem cells share identical genomic sequences with other lineage-committed cells yet possess the remarkable properties of self-renewal and pluripotency. It has been proposed that epigenetic regulatory mechanisms, involving DNA methylation and various chromatin modifications, are at least partly responsible for the distinct cellular properties between different cell types. Previous studies focusing largely on gene promoters and CpG islands have identified close association between several chromatin modifications and DNA methylation, but revealed a relatively small degree of differences between pluripotent and lineage-committed cells. Here, we examine the association between 11 chromatin modifications and DNA methylation at high resolution throughout the genome in the human embryonic stem cells and primary fetal lung fibroblasts. We observe a new set of relationships between chromatin modifications and DNA methylation occurring outside of the promoter regions. We also find that epigenomic landscapes are drastically different between the ES cells and fibroblasts. In particular, over 40% of the human genome differs in their chromatin structure between the two cell types. Most of the changes come from a dramatic redistribution of the repressive H3K9me3 and H3K27me3 marks, which form large blocks that expand significantly in the fibroblasts relative to ES cells. Additionally, we identified numerous small and punctuated regions outside of promoters that are associated with many active chromatin modification marks, and show that chromatin dynamics at these potential regulatory sequences are associated with change in DNA methylation between the ES cells and fibroblasts. Our results provide new insights into epigenetic regulatory mechanisms underlying properties of pluripotency and cell fate commitment. ChIP-Seq Analysis of OCT4, KLF4, MYC, TAFII and P300 in hESC H1 cells. 36 cycles of sequencing was done on the Illumina Genome Analyzer or Analyzer II platforms.

Dataset Information

Regulatory element copy number differences shape primate expression profiles.

Publications

Regulatory element copy number differences shape primate expression profiles.

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