Hairy/enhancer-of-split related with YRPW motif protein 2 (HEY2) also known as cardiovascular helix-loop-helix factor 1 (CHF1) is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

that in humans is encoded by the ''HEY2''

gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

. This protein is a type of

transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The f ...

that belongs to the hairy and enhancer of split-related (HESR) family of basic helix-loop-helix ( bHLH)-type

s. It forms homo- or hetero-dimers that localize to the nucleus and interact with a histone deacetylase complex to repress

transcription Transcription refers to the process of converting sounds (voice, music etc.) into letters or musical notes, or producing a copy of something in another medium, including: Genetics * Transcription (biology), the copying of DNA into RNA, the fir ...

. 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. 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 and

somitogenesis Somitogenesis is the process by which somites form. Somites are bilaterally paired blocks of paraxial mesoderm that form along the anterior-posterior axis of the developing embryo in segmented animals. In vertebrates, somites give rise to skelet ...

. 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 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 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 Sodium channel protein type 5 subunit alpha, also known as NaV1.5 is an integral membrane protein and tetrodotoxin-resistant voltage-gated sodium channel subunit. NaV1.5 is found primarily in cardiac muscle, where it mediates the fast influx of N ...

SCN10A Nav1.8 is a sodium ion channel subtype that in humans is encoded by the ''SCN10A'' gene. Nav1.8-containing channels are tetrodotoxin (TTX)-resistant voltage-gated channels. Nav1.8 is expressed specifically in the dorsal root ganglion (DRG), in u ...

, and HEY2 (this gene) are associated with Brugada syndrome.

Interactions

HEY2 has been shown to

interact Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...

with Sirtuin 1 and

Nuclear receptor co-repressor 1 The nuclear receptor co-repressor 1 also known as thyroid-hormone- and retinoic-acid-receptor-associated co-repressor 1 (TRAC-1) is a protein that in humans is encoded by the ''NCOR1'' gene. NCOR1 is a transcriptional coregulatory protein which c ...

References

External links