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. 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. The origin of the term "housekeeping gene" remains obscure. Literature from 1976 used the term to describe specifically tRNA and rRNA. 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. In Drosophila, where promoter specific CpG Islands are absent, housekeeping gene promoters contain DNA elements like DRE, E-box or DPE. 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. 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. Furthermore, housekeeping promoters are regulated by housekeeping enhancers but not developmentally regulated enhancers.

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

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

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