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Series GSE16546 Query DataSets for GSE16546
Status Public on Jun 10, 2009
Title Definition, conservation and epigenetics of housekeeping and tissue-enriched genes
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Housekeeping genes (HKG) are constitutively expressed in all tissues while tissue-enriched genes (TEG) are expressed at a much higher level in a single tissue type than in others. HKGs serve as valuable experimental controls in gene and protein expression experiments, while TEGs tend to represent distinct physiological processes and are frequently candidates for biomarkers or drug targets. The genomic features of these two groups of genes expressed in opposing patterns may shed light on the mechanisms by which cells maintain basic and tissue-specific functions.

Here, we generate gene expression profiles of 42 normal human tissues on custom high-density microarrays to systematically identify 1,522 HKGs and 975 TEGs and compile a small subset of 20 housekeeping genes which are highly expressed in all tissues with lower variance than many commonly used HKGs. Cross-species comparison shows that both the functions and expression patterns of HKGs are conserved. TEGs are enriched with respect to both segmental duplication and copy number variation, while no such enrichment is observed for HKGs, suggesting the high expression of HKGs are not due to high copy numbers. Analysis of genomic and epigenetic features of HKGs and TEGs reveals that the high expression of HKGs across different tissues is associated with decreased nucleosome occupancy at the transcription start site as indicated by enhanced DNase hypersensitivity. Additionally, we systematically and quantitatively demonstrated that the CpG islands' enrichment in HKGs transcription start sites (TSS) and their depletion in TEGs TSS. Histone methylation patterns differ significantly between HKGs and TEGs, suggesting that methylation contributes to the differential expression patterns as well.We have compiled a set of high quality HKGs that should provide higher and more consistent expression when used as references in laboratory experiments than currently used HKGs. The comparison of genomic features between HKGs and TEGs shows that HKGs are more conserved than TEGs in terms of functions, expression pattern and polymorphisms. In addition, our results identify chromatin structure and epigenetic features of HKGs and TEGs that are likely to play an important role in regulating their strikingly different expression patterns.
 
Overall design We performed microarray experiment on more tissues and probesets in additional to the previous GEO submission (Series GSE11863). In brief, PolyA+ purified RNA pooled from multiple donors of a single human tissue type (e.g. cerebellum) were amplified with random primers and hybridized on a two-color ink-jet oligonucletodie microarray against a common reference pool, comprising ~20 normal adult tissue pools, on custom microarray patterns containing probes to monitor every exon and exon-exon junction in transcript databases, patent databases, and predicted from mouse transcripts. Data were analyzed for gene expression (the average of multiple probes), exon and junction expression, and splice form proportionality.
 
Citation(s) 19534766
Submission date Jun 10, 2009
Last update date Jan 18, 2013
Contact name Amit V Kulkarni
E-mail(s) amit_kulkarni@merck.com
Phone 206-802-7352
Organization name Rosetta Inpharmatics / Merck Pharmaceuticals
Department Genomics
Lab Array Design
Street address 401 Terry Ave N
City Seattle
State/province WA
ZIP/Postal code 98109
Country USA
 
Platforms (26)
GPL6826 Rosetta/Merck DT_Phase2_1_of_17 microarray
GPL6827 Rosetta/Merck DT_Phase2_2_of_17 microarray
GPL6828 Rosetta/Merck DT_Phase2_3_of_17 microarray
Samples (564)
GSM294996 Adipose vs pool
GSM294997 Adipose vs pool
GSM294998 Adipose vs pool
Relations
BioProject PRJNA116173

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Supplementary file Size Download File type/resource
GSE16546_RAW.tar 128.9 Mb (http)(custom) TAR
Processed data included within Sample table
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