D site of albumin promoter (albumin D-box) binding protein, also known as DBP, is a protein which in humans is encoded by the ''DBP''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
DBP is a member of the PAR bZIP (Proline and Acidic amino acid-Rich basic leucine ZIPper)
transcription factor
In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription (genetics), transcription of genetics, genetic information from DNA to messenger RNA, by binding t ...
family.
DBP binds to an upstream promoter in the
insulin
Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the insulin (''INS)'' gene. It is the main Anabolism, anabolic hormone of the body. It regulates the metabol ...
gene.
DBP was shown to follow a stringent circadian rhythm;
both the levels of protein and
mRNA
In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein.
mRNA is ...
are almost non-detectable in the morning, but reach their maximum level in the evening.
Discovery of circadian rhythm of expression
The circadian rhythm of the expression of DBP was
discovered by chance in the laboratory of
Ueli Schibler at the
University of Geneva
The University of Geneva (French: ''Université de Genève'') is a public university, public research university located in Geneva, Switzerland. It was founded in 1559 by French theologian John Calvin as a Theology, theological seminary. It rema ...
in 1990. A
canadian
Canadians () are people identified with the country of Canada. This connection may be residential, legal, historical or cultural. For most Canadians, many (or all) of these connections exist and are collectively the source of their being ''C ...
postdoc working in the lab, Chris Mueller, had identified the DBP transcription factor.
However, when a new PhD student in the lab, Jérôme Wuarin, took over the project on DBP, he failed to observe any expression of the protein, and initially thought that the original experiment was flawed. It was later discovered that the two researchers were working at different times of the day: Chris Mueller was a night owl and a late riser, and would isolate the transcription factor by mid-afternoon, while Jérôme Wuarin was an early riser and obtained the sample at 7:00. Following this discovery, Jérôme Wuarin repeated the experiment every 4 hour during a full day, and found that the expression of DBP changed by a 100-fold factor over the day, ranging from being undetectable in the morning to being easy to find in the afternoon.
While many genes have been found to be transcribed rhythmically since this discovery, DBP remains the one that has the largest amplitude between its minimum and maximum expression.
While the researchers initially thought that the underlying mechanism was the rhythmic secretion of
hormones
A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs or tissues by complex biological processes to regulate physiology and behavior. Hormones a ...
, it became clear that the rhythmic expression of DBP was driven instead by cell-autonomous
oscillators
Oscillation is the repetitive or periodic variation, typically in time, of some measure about a central value (often a point of equilibrium) or between two or more different states. Familiar examples of oscillation include a swinging pendulum ...
that are entrained by the master clock in the
Suprachiasmatic Nucleus
The suprachiasmatic nucleus or nuclei (SCN) is a small region of the brain in the hypothalamus, situated directly above the optic chiasm. It is responsible for regulating sleep cycles in animals. Reception of light inputs from photosensitive r ...
(SCN). Schibler and his colleagues followed this line of inquiry into the field of chronobiology.
References
Further reading
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External links
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Transcription factors
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