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Cited by 173Genomics and Chromatin DynamicsGene expression and cancer classificationEpigenetics and DNA Methylation

Definition, conservation and epigenetics of housekeeping and tissue-enriched genes

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She, Xinwei, Rohl, Carol A, Castle, John C, Kulkarni, Amit V, Johnson, Jason M, Chen, Ronghua·2009·BMC Genomics
DOI 10.1186/1471-2164-10-269PMC PMC2706266
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Abstract

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 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. CONCLUSION: 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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  • UCOEs were found to be helpful for increasing the productivity of recombinant protein cell lines.

    “UCOEs were also found to be helpful for increasing the productivity of recombinant protein cell lines (Benton et al., 2002;She et al., 2009).”

    From Therapeutic glycoprotein production in mammalian cells (2017) · cites this paper as She et al., 2009

    The Results and Discussion section on ultraconserved elements discusses UCEs and their enrichment in housekeeping genes, not UCOEs. Searches for UCOEs and recombinant-protein cell-line productivity found no passage in our copy addressing the claimed benefit. (LLM, conf=0.78)

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Cited by

Sorted by citations

Authors
She, X., Rohl, C. A., Castle, J. C., Kulkarni, A. V., Johnson, J. M., & Chen, R.
Affiliations
Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
Corresponding author
  • She, Xinwei
  • Chen, Ronghua
ORCID
Venue
BMC Genomics
Publisher
Springer Science and Business Media LLC
Published
2009
Volume
10
Issue
1
Pages
269
ISSN
1471-2164 (ISSN-L)
DOI
10.1186/1471-2164-10-269
PMC
PMC2706266
OpenAlex
W2132448421
Cited by
173
References
2
Citations by year
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FWCI
4.16
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • BMC Genomics (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene expression and cancer classification
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Keywords
housekeeping genes, tissue-specific gene expression, gene expression profiling, cross-species conservation, segmental duplication, copy number variation, DNase hypersensitivity, nucleosome occupancy, CpG islands, histone methylation, chromatin structure, epigenetics
MeSH terms
Chromatin, Gene Expression Regulation, Humans, Genome, Human, Conserved Sequence, Gene Dosage, CpG Islands, DNA Methylation, Oligonucleotide Array Sequence Analysis, Gene Duplication, Gene Expression Profiling, Transcription Initiation Site, Epigenesis, Genetic

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