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| Status |
Public on Mar 01, 2011 |
| Title |
Definition, conservation and epigenetics of housekeeping and tissue-enriched genes |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Background
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.
Results
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 that can be used as experimental reference and are superior to 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.
Conclusions
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.
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| Overall design |
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. Total 42 normal human tissues were testes against the pools.
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| |
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| Citation(s) |
19534766 |
| |
| Submission date |
Feb 20, 2009 |
| Last update date |
Mar 20, 2012 |
| Contact name |
Xinwei She |
| E-mail(s) |
xinwei_she@merck.com
|
| Phone |
206-802-6422
|
| Fax |
206-802-6411
|
| Organization name |
Rosetta Inpharmatics, Merck
|
| Department |
Molecular Informatics
|
| Street address |
401 Terry Ave. N
|
| City |
Seattle |
| State/province |
WA |
| ZIP/Postal code |
98109 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL8217 |
Rosetta Human Gene Expression Array |
|
| Samples (42)
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| Relations |
| BioProject |
PRJNA111981 |
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