Housekeeping gene explained

In molecular biology, housekeeping genes are typically constitutive genes that are required for the maintenance of basic cellular function, and are expressed in all cells of an organism under normal and patho-physiological conditions.[1] [2] [3] Although some housekeeping genes are expressed at relatively constant rates in most non-pathological situations, the expression of other housekeeping genes may vary depending on experimental conditions.[4]

The origin of the term "housekeeping gene" remains obscure. Literature from 1976 used the term to describe specifically tRNA and rRNA.[5] For experimental purposes, the expression of one or multiple housekeeping genes is used as a reference point for the analysis of expression levels of other genes. The key criterion for the use of a housekeeping gene in this manner is that the chosen housekeeping gene is uniformly expressed with low variance under both control and experimental conditions. Validation of housekeeping genes should be performed before their use in gene expression experiments such as RT-PCR. Recently a web-based database of human and mouse housekeeping genes and reference genes/transcripts, named Housekeeping and Reference Transcript Atlas (HRT Atlas), was developed to offer updated list of housekeeping genes and reliable candidate reference genes/transcripts for RT-qPCR data normalization. This database can be accessed at http://www.housekeeping.unicamp.br.

Housekeeping gene regulation

Housekeeping genes account for majority of the active genes in the genome, and their expression is obviously vital to survival. The housekeeping gene expression levels are fine-tuned to meet the metabolic requirements in various tissues. Biochemical studies on transcription initiation of the housekeeping gene promoters have been difficult, partly due to the less-characterized promoter motifs and transcription initiation process.

Human housekeeping gene promoters are generally depleted of TATA-box, have high GC content and high incidence of CpG Islands.[6] In Drosophila, where promoter specific CpG Islands are absent, housekeeping gene promoters contain DNA elements like DRE, E-box or DPE.[7] Transcription start sites of housekeeping genes can span over a region of around 100 bp whereas transcription start sites of developmentally regulated genes are usually focused in a narrow region.[8] [9] [10] Little is known about how the dispersed transcription initiation of housekeeping gene is established. There are transcription factors that are specifically enriched on and regulate housekeeping gene promoters.[11] [12] Furthermore, housekeeping promoters are regulated by housekeeping enhancers but not developmentally regulated enhancers.[13]

Common housekeeping genes in humans

The following is a partial list of "housekeeping genes." For a more complete and updated list, see HRT Atlas database compiled by Bidossessi W. Hounkpe et al. The database was constructed by mining more than 12000 human and mouse RNA-seq datasets.

Gene expression

Transcription factors

Repressors

RNA splicing

Translation factors

tRNA synthesis
RNA binding protein

Ribosomal proteins

RPS19BP1

Mitochondrial ribosomal proteins

RNA polymerase

Protein processing

Heat shock proteins

Histone

Cell cycle

There is significant overlap in function with regards to some of these proteins. In particular, the Rho-related genes are important in nuclear trafficking (i.e.: mitosis) as well as with mobility along the cytoskeleton in general. These genes of particular interest in cancer research.

Apoptosis

Oncogenes

DNA repair/replication

Metabolism

Carbohydrate metabolism

[16]

Citric Acid Cycle

Lipid metabolism

Amino acid metabolism

NADH dehydrogenase

Cytochrome C oxidase

(Note that COX1, COX2, and COX3 are mitochondrially encoded)

ATPase

Lysosome

Proteasome

Ribonuclease

Thioreductase

Structural

Cytoskeletal

[17] [15] [18]

Organelle synthesis

A specialized form of cell signaling

Mitochondrion

Surface

Cell adhesion

Channels and transporters

Receptors

HLA/immunoglobulin/cell recognition

Kinases/signalling

Growth factors

Tissue necrosis factor

Casein kinase

Miscellaneous

Open_reading_frame

Sperm/Testis

Although this page is devoted to genes that should be ubiquitously expressed, this section is for genes whose current name reflects their relative upregulation in testes

See also

External links

Notes and References

  1. Hounkpe. Bidossessi Wilfried. Chenou. Francine. de-Lima. Franciele. De-Paula. Erich Vinicius. 2020-07-14. HRT Atlas v1.0 database: redefining human and mouse housekeeping genes and candidate reference transcripts by mining massive RNA-seq datasets. Nucleic Acids Research. 49. D1. en. D947–D955. 10.1093/nar/gkaa609 . 32663312. 7778946 . 0305-1048. free.
  2. Butte AJ, Dzau VJ, Glueck SB . Further defining housekeeping, or "maintenance," genes Focus on "A compendium of gene expression in normal human tissues" . Physiological Genomics . 7 . 2 . 95–96 . December 2001 . 11773595 . 10.1152/physiolgenomics.2001.7.2.95 .
  3. Zhu J, He F, Hu S, Yu J . On the nature of human housekeeping genes . Trends in Genetics . 24 . 10 . 481–484 . October 2008 . 18786740 . 10.1016/j.tig.2008.08.004 .
  4. Greer S, Honeywell R, Geletu M, Arulanandam R, Raptis L . Housekeeping genes; expression levels may change with density of cultured cells . Journal of Immunological Methods . 355 . 1–2 . 76–79 . April 2010 . 20171969 . 10.1016/j.jim.2010.02.006 .
  5. Rifkind RA, Marks PA, Bank A, Terada M, Maniatis GM, Reuben R, Fibach E . Erythroid differentiation and the cell cycle: some implications from murine foetal and erythroleukemic cells . Annales d'Immunologie . 127 . 6 . 887–893 . Nov–Dec 1976 . 1070288 .
  6. Smale ST, Kadonaga JT . The RNA polymerase II core promoter . Annual Review of Biochemistry . 72 . 449–479 . 2003 . 12651739 . 10.1146/annurev.biochem.72.121801.161520 .
  7. Rach EA, Winter DR, Benjamin AM, Corcoran DL, Ni T, Zhu J, Ohler U . Transcription initiation patterns indicate divergent strategies for gene regulation at the chromatin level . PLOS Genetics . 7 . 1 . e1001274 . January 2011 . 21249180 . 3020932 . 10.1371/journal.pgen.1001274 . free .
  8. Ni T, Corcoran DL, Rach EA, Song S, Spana EP, Gao Y, Ohler U, Zhu J . A paired-end sequencing strategy to map the complex landscape of transcription initiation . Nature Methods . 7 . 7 . 521–527 . July 2010 . 20495556 . 3197272 . 10.1038/nmeth.1464 .
  9. Carninci P, Sandelin A, Lenhard B, Katayama S, Shimokawa K, Ponjavic J, Semple CA, Taylor MS, Engström PG, Frith MC, Forrest AR, Alkema WB, Tan SL, Plessy C, Kodzius R, Ravasi T, Kasukawa T, Fukuda S, Kanamori-Katayama M, Kitazume Y, Kawaji H, Kai C, Nakamura M, Konno H, Nakano K, Mottagui-Tabar S, Arner P, Chesi A, Gustincich S, Persichetti F, Suzuki H, Grimmond SM, Wells CA, Orlando V, Wahlestedt C, Liu ET, Harbers M, Kawai J, Bajic VB, Hume DA, Hayashizaki Y . 6 . Genome-wide analysis of mammalian promoter architecture and evolution . Nature Genetics . 38 . 6 . 626–635 . June 2006 . 16645617 . 10.1038/ng1789 . 22205897 .
  10. Hoskins RA, Landolin JM, Brown JB, Sandler JE, Takahashi H, Lassmann T, Yu C, Booth BW, Zhang D, Wan KH, Yang L, Boley N, Andrews J, Kaufman TC, Graveley BR, Bickel PJ, Carninci P, Carlson JW, Celniker SE . 6 . Genome-wide analysis of promoter architecture in Drosophila melanogaster . Genome Research . 21 . 2 . 182–192 . February 2011 . 21177961 . 3032922 . 10.1101/gr.112466.110 .
  11. Lam KC, Mühlpfordt F, Vaquerizas JM, Raja SJ, Holz H, Luscombe NM, Manke T, Akhtar A . 6 . The NSL complex regulates housekeeping genes in Drosophila . PLOS Genetics . 8 . 6 . e1002736 . 2012 . 22723752 . 3375229 . 10.1371/journal.pgen.1002736 . free .
  12. Lam KC, Chung HR, Semplicio G, Iyer SS, Gaub A, Bhardwaj V, Holz H, Georgiev P, Akhtar A . 6 . The NSL complex-mediated nucleosome landscape is required to maintain transcription fidelity and suppression of transcription noise . Genes & Development . 33 . 7–8 . 452–465 . February 2019 . 30819819 . 6446542 . 10.1101/gad.321489.118 .
  13. Zabidi MA, Arnold CD, Schernhuber K, Pagani M, Rath M, Frank O, Stark A . Enhancer-core-promoter specificity separates developmental and housekeeping gene regulation . Nature . 518 . 7540 . 556–559 . February 2015 . 25517091 . 6795551 . 10.1038/nature13994 . 2015Natur.518..556Z .
  14. Hsiao LL, Dangond F, Yoshida T, Hong R, Jensen RV, Misra J, Dillon W, Lee KF, Clark KE, Haverty P, Weng Z, Mutter GL, Frosch MP, MacDonald ME, Milford EL, Crum CP, Bueno R, Pratt RE, Mahadevappa M, Warrington JA, Stephanopoulos G, Stephanopoulos G, Gullans SR . 6 . A compendium of gene expression in normal human tissues . Physiological Genomics . 7 . 2 . 97–104 . December 2001 . 11773596 . 10.1152/physiolgenomics.00040.2001 . 10.1.1.333.2656 .
  15. RT2 Profiler PCR Array (96-Well Format and 384-Well Format. Qiagen Catalog No. 330231 PAHS-00ZA. Quiagen.
  16. Velculescu VE, Madden SL, Zhang L, Lash AE, Yu J, Rago C, Lal A, Wang CJ, Beaudry GA, Ciriello KM, Cook BP, Dufault MR, Ferguson AT, Gao Y, He TC, Hermeking H, Hiraldo SK, Hwang PM, Lopez MA, Luderer HF, Mathews B, Petroziello JM, Polyak K, Zawel L, Kinzler KW . Analysis of human transcriptomes . Nature Genetics . 23 . 4 . 387–388 . December 1999 . 10581018 . 10.1038/70487 . 29173492 .
  17. Eisenberg E, Levanon EY . Human housekeeping genes are compact . Trends in Genetics . 19 . 7 . 362–365 . July 2003 . 12850439 . 10.1016/S0168-9525(03)00140-9 . q-bio/0309020 . 2003q.bio.....9020E . 7728312 .
  18. Caradec J, Sirab N, Keumeugni C, Moutereau S, Chimingqi M, Matar C, Revaud D, Bah M, Manivet P, Conti M, Loric S . 'Desperate house genes': the dramatic example of hypoxia . British Journal of Cancer . 102 . 6 . 1037–1043 . March 2010 . 20179706 . 2844028 . 10.1038/sj.bjc.6605573 .

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