Hairy/enhancer-of-split related with YRPW motif protein 2 (HEY2) also known as cardiovascular helix-loop-helix factor 1 (CHF1) is a protein that in humans is encoded by the ''HEY2'' gene. This protein is a type of transcription factor that belongs to the hairy and enhancer of split-related (HESR) family of basic helix-loop-helix ( bHLH)-type transcription factors. It forms homo- or hetero-dimers that localize to the nucleus and interact with a

histone deacetylase Histone deacetylases (, HDAC) are a class of enzymes that remove acetyl groups (O=C-CH3) from an ε-N-acetyl lysine amino acid on a histone, allowing the histones to wrap the DNA more tightly. This is important because DNA is wrapped around his ...

complex to repress transcription. During embryonic development, this mechanism is used to control the number of cells that develop into cardiac progenitor cells and myocardial cells. The relationship is inversely related, so as the number of cells that express the Hey2 gene increases, the more CHF1 is present to repress transcription and the number of cells that take on a myocardial fate decreases.

Expression

The expression of the Hey2 gene is induced by the

Notch signaling pathway The Notch signaling pathway is a highly Conserved sequence, conserved cell signaling system present in most animals. Mammals possess four different Notch proteins, notch receptors, referred to as NOTCH1, NOTCH2, Notch 3, NOTCH3, and NOTCH4. The ...

. In this mechanism, adjacent cells bind via transmembrane notch receptors. Two similar and redundant genes in mouse are required for embryonic cardiovascular development, and are also implicated in

neurogenesis Neurogenesis is the process by which nervous system cells, the neurons, are produced by neural stem cells (NSCs). It occurs in all species of animals except the porifera (sponges) and placozoans. Types of NSCs include neuroepithelial cells (NECs) ...

and somitogenesis. Alternatively spliced transcript variants have been found, but their biological validity has not been determined.

Knockout studies

The Hey2 gene is involved with the formation of the

cardiovascular system The blood circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the entire body of a human or other vertebrate. It includes the cardiovascular system, or vascular system, tha ...

and especially the heart itself. Although studies have not been conducted about the effects of a malfunction in Hey2 expression in humans, experiments done with mice suggest this gene could be responsible for a number of heart defects. Using a

gene knockout A gene knockout (abbreviation: KO) is a genetic technique in which one of an organism's genes is made inoperative ("knocked out" of the organism). However, KO can also refer to the gene that is knocked out or the organism that carries the gene kno ...

technique, scientists inactivated both the Hey1 and Hey2 genes of mice. The loss of these two genes resulted in death of the embryo 9.5 days after conception. It was found that the developing hearts of these embryos lacked most structural formations which resulted in massive hemorrhage. When only the Hey1 gene was knocked out, no apparent phenotypic changes occurred, suggesting that these two genes carry similar and redundant information for the development of the heart.

Clinical significance

Common variants of SCN5A, SCN10A, and HEY2 (this gene) are associated with

Brugada syndrome Brugada syndrome (BrS) is a genetic disorder in which the electrical activity of the heart is abnormal due to channelopathy. It increases the risk of abnormal heart rhythms and sudden cardiac death. Those affected may have episodes of syncope ...

Interactions

HEY2 has been shown to interact with

Sirtuin 1 Sirtuin 1, also known as NAD-dependent deacetylase sirtuin-1, is a protein that in humans is encoded by the SIRT1 gene. SIRT1 stands for sirtuin (silent mating type information regulation 2 homolog) 1 (''S. cerevisiae''), referring to the fact t ...

and Nuclear receptor co-repressor 1.

References

External links