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 residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
that in humans is encoded by the ''HEY2''
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 ...
.
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 (genetics), transcription of genetics, genetic information from DNA to messenger RNA, by binding t ...
that belongs to the hairy and enhancer of split-related (HESR) family of basic helix-loop-helix (
bHLH)-type
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 ...
s. 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 both histone and non-histone proteins. HDACs allow histones to wrap the DNA more tightly. This is important becaus ...
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, often th ...
. 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 animal, animals. Mammals possess four different Notch proteins, notch receptors, referred to as NOTCH1, NOTCH2, Notch 3, NOTCH3, and NOTC ...
. 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). This occurs in all species of animals except the porifera (sponges) and placozoans. Types of NSCs include neuroepithelial cells ( ...
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 vertebrates. The somites give rise to skeletal muscle, cartila ...
. 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
In vertebrates, the circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the body. It includes the cardiovascular system, or vascular system, that consists of the heart a ...
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
Gene knockouts (also known as gene deletion or gene inactivation) are a widely used genetic engineering technique that involves the gene targeting, targeted removal or inactivation of a specific gene within an organism's genome. This can be done t ...
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 ...
,
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 ...
, 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 advocating for the legal and human rights of children with intersex traits. The organization was founded in 2006 and fo ...
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 f ...
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
Further reading
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External links
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{{Transcription factors, g1
Transcription factors