PER2

Key takeaways

PER2 belongs to biology; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect PER2 to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of PER2 from memory before moving on to harder problems.

Reference excerpt

PER2 is a protein in mammals encoded by the PER2 gene. PER2 is noted for its major role in circadian rhythms.

Discovery The per gene was first discovered using forward genetics in Drosophilla melanogaster in 1971. Mammalian Per2 was discovered by in 1997 through a search for homologous cDNA sequences to PER1. It is more similar to Drosophila per than its paralogs. Later experiments in also identified Per2 in humans.

Function PER2 is a member of the Period family of genes and is expressed in a circadian pattern in the suprachiasmatic nucleus, the primary circadian pacemaker in the mammalian brain. Genes in this family encode components of the circadian clock, which regulates the daily rhythms of locomotor activity, metabolism, and behavior. Circadian expression of these genes and their encoded proteins in the suprachiasmatic nucleus. Human PER2 is involved in human sleep disorders and cancer formation. Lowered PER2 expression is common in many tumors cells within the body, suggesting PER2 is integral for proper function and decreased levels promotes tumor progression. PER2 contains glucocorticoid response elements (GREs) and a GRE within the core clock gene PER2 is continuously occupied during rhythmic expression and essential for glucocorticoid regulation of PER2 in vivo. Mice with a genomic deletion spanning this GRE expressed elevated leptin levels and were protected from glucose intolerance and insulin resistance on glucocorticoid treatment but not from muscle wasting. PER2 is an integral component of a particular glucocorticoid regulatory pathway and that glucocorticoid regulation of the peripheral clock is selectively required for some actions of glucocorticoids. PER2 expression in mice is increased by exposure to 13,000 lumens of intense daylight such as sunshine while decreasing troponin levels in equal opposite amounts. PER2 in turn enhances oxygen-efficient glycolysis and hence provides cardioprotection from ischemia. Therefore, it is speculated that strong light may reduce the risk of heart attacks and decrease the damage after experiencing one. Moreover, PER2 has protective functions in liver diseases, as it antagonizes hepatitis C viral replication. Per2 knockout mice experience a free-running period of around 21.8 hours, compared to the normal mouse free-running period of 23.3 hours. Some of the Per2 knockout mice can also become arrhythmic under constant light conditions. PER2 has also been shown to be possibly important in the development of cancer. PER2 expression is significantly lower in human patients with lymphoma and acute myeloid leukemia. The PER2 protein seems to be important for the proliferation of osteoblasts, which aid in adding density to the bone through a pathway utilizing Myc and Ccnd1. Certain PER2 mutations have shown that they can increase the tolerance to the amount of alcohol that a mouse can intake through reduced uptake of glutamate.

Main interactions In mammals, mPER2 forms a heterodimer with mPER1, mCRY1, and mCRY2 by binding to PAS domains. The heterodimer acts to inhibit their own transcription by suppressing the CLOCK/BMAL1 complex resulting in a negative feedback loop. This negative feedback loop is essential for maintaining a functioning circadian clock. A disruption of either both mPER1 and mPER2 genes together or both mCRY genes causes behavioural arrhythmicity when the double-knockout animals are placed in constant conditions. A third PER gene, mPer3, does not have a critical role in the maintenance of the core clock feedback loops. Molecular and behavioural rhythms are preserved in mice lacking mPer3.

Interactions with CK1e PER2 has been shown to interact with a kinase called CK1e. CK1e phosphorylates PER2 in mammals. In Syrian hamster, a mutation called tau has been discovered in the CK1e, which increases phosphorylation of homologous PER2 leading to a faster degradation and a shortened period. Mutations in hPER2 can cause FASPS because of a lack of phosphorylation site in the mutated hPER2 protein.

Interaction table

Clinical significance A genetic test from a cheek swab can use PER2 expression levels to tell whether a person is an early morning person or a "night owl".

Familial advanced sleep phase Familial advanced sleep phase (FASP) is characterized as a short period (e.g. 23.3 vs 24.3hr for population) in humans. A mutation in hPER2 decreases its phosphorylation by CK1d, which causes the phenotype seen in some FASP. The primary cause of these FASP is a mutation that changes amino acid 662 from serine to glycine (S662G) in PER2. The S662G mutation makes PER2 mutant protein a stronger repressor than normal PER2, decreasing cellular PER2 levels and therefore causing this form of FASP. The mutation also seems to cause an increase in the turnover rate of PER2 in the nucleus.

Gene The PER2 gene is located on the long (q) arm of chromosome 2 at position 37.3 and has 25 exons. Predicted human PER2 protein created from the PER2 gene shares 44% identity with human PER1 and 77% identity with mouse Per2. Northern blots analysis revealed that PER2 was expressed as a 7-kb mRNA in all tissues examined. An additional 1.8-kb transcript was also detected in some tissues. PER2 mRNA has been shown to peak at ZT 6 in the SCN.

See also PER1 PER3 Familial sleep traits

References

Illustrations

Worked examples

Example 1 — a first encounter with PER2

Start with the simplest possible case. Write down what PER2 claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In biology, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to PER2 before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about PER2 ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of PER2

In research: PER2 appears in biology research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses PER2 in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: PER2 is common in secondary-school and first-year university syllabi. It links to neighbouring topics Genes on human chromosome 2, PAS-domain-containing proteins, Transcription factors, so understanding it makes those chapters shorter.
In everyday life: Look for PER2 outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

How to study PER2 in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what PER2 means in your own words.
Compare your version with the excerpt and mark what you missed.
Work through the three examples above with pen and paper.
Explain PER2 out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is PER2 in simple terms?

PER2 is a protein in mammals encoded by the PER2 gene. PER2 is noted for its major role in circadian rhythms.

Why does PER2 matter?

Because it connects several biology ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study PER2?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on PER2.