This article is about the general topic of housekeeping genes. For a list of housekeeping genes that should be used as reference standard, see
reference genes.
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][4] 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.[1][5]
The origin of the term "housekeeping gene" remains obscure. Literature from 1976 used the term to describe specifically
tRNA and
rRNA.[6] 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.[1] 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.[7] In Drosophila, where
promoter specific CpG Islands are absent, housekeeping gene promoters contain DNA elements like DRE, E-box or DPE.[8] 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.[9][10][11] 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.[12][13] Furthermore, housekeeping promoters are regulated by housekeeping
enhancers but not developmentally regulated enhancers.[14]
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.[1] The database was constructed by mining more than 12000 human and mouse RNA-seq datasets.[1]
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.
RAB10 NM_016131 The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes
CCNB1IP1 NM_021178 E3 ubiquitin-protein ligase. Modulates cyclin B levels and participates in the regulation of cell cycle progression through the G2 phase
CCNDBP1 NM_012142 May negatively regulate cell cycle progression
CCNG1 NM_004060 May play a role in growth regulation
CCNH NM_001239 Involved in cell cycle control and in RNA transcription by RNA polymerase II. Its expression and activity are constant throughout the cell cycle
CCNK NM_001099402 Regulatory subunit of cyclin-dependent kinases that mediates phosphorylation of the large subunit of RNA polymerase II
CCNL1 NM_020307 Transcriptional regulator which participates in regulating the pre-mRNA splicing process
CCNL2 NM_030937 Transcriptional regulator which participates in regulating the pre-mRNA splicing process. Also modulates the expression of critical apoptotic factor, leading to cell apoptosis.
CCNY NM_145012 Positive regulatory subunit of the cyclin-dependent kinases CDK14/PFTK1 and CDK16. Acts as a cell-cycle regulator of Wnt signaling pathway during G2/M phase
PPP1CA NM_002708 Protein phosphatase that associates with over 200 regulatory proteins to form highly specific holoenzymes which dephosphorylate hundreds of biological targets
XRCC6 NM_001469 Homo sapiens thyroid autoantigen: Single-stranded DNA-dependent ATP-dependent helicase. Has a role in chromosome translocation.
Metabolism
PRKAG1[2]Senses energy level and inactivates HMGCoA reductase and Acetyl CoA Carboxylase
PRKAA1 NM_006251 Catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism
PRKAB1 NM_006253 Non-catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism
PRKACA NM_002730 Phosphorylates a large number of substrates in the cytoplasm and the nucleus.
PRKAG1 NM_002733 Homo sapiens protein kinase, AMP-activated, gamma 1 non-catalytic subunit (PRKAG1), mRNA
PRKAR1A NM_002734 Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells
SDHB NM_002973 Iron-sulfur protein (IP) subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q)
SDHC NM_003000 Membrane-anchoring subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q).
UQCC NM_018244 Required for the assembly of the ubiquinol-cytochrome c reductase complex (mitochondrial respiratory chain complex III or cytochrome b-c1 complex)
RPA2[2] Binds DNA during replication to keep it straightened out
SULT1A3[2] Sulfate conjugation (note: SULT1C is cited in earlier literature as being ubiquitous [15] but this may be an example of different tags being used to refer to a common area of 2 closely related genes. If the tag is too short, then it may not be specific enough to truly specify one member of a gene family from another)
SYNGR2[2][15] Synaptogyrin (may participate in vesicle translocation)
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
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^Zhu J, He F, Hu S, Yu J (October 2008). "On the nature of human housekeeping genes". Trends in Genetics. 24 (10): 481–484.
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^Greer S, Honeywell R, Geletu M, Arulanandam R, Raptis L (April 2010). "Housekeeping genes; expression levels may change with density of cultured cells". Journal of Immunological Methods. 355 (1–2): 76–79.
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^Rifkind RA, Marks PA, Bank A, Terada M, Maniatis GM, Reuben R, Fibach E (Nov–Dec 1976). "Erythroid differentiation and the cell cycle: some implications from murine foetal and erythroleukemic cells". Annales d'Immunologie. 127 (6): 887–893.
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