HEY2

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HEY2
Identifiers
AliasesHEY2, CHF1, GRIDLOCK, GRL, HERP1, HESR2, HRT2, bHLHb32, hes related family bHLH transcription factor with YRPW motif 2
External IDsMGI: 1341884 HomoloGene: 22705 GeneCards: HEY2
Gene location (Human)
Chromosome 6 (human)
Chr.Chromosome 6 (human)[1]
Chromosome 6 (human)
Genomic location for HEY2
Genomic location for HEY2
Band6q22.31Start125,747,664 bp[1]
End125,761,269 bp[1]
RNA expression pattern
PBB GE HEY2 219743 at fs.png
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_012259

NM_013904

RefSeq (protein)

NP_036391

NP_038932

Location (UCSC)Chr 6: 125.75 – 125.76 MbChr 10: 30.83 – 30.84 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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.[5][6]

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 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. [7] 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. [7]

Expression[edit]

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. Alternatively spliced transcript variants have been found, but their biological validity has not been determined.[6]

Knockout studies[edit]

The Hey2 gene is involved with the formation of the cardiovascular system and especially the heart itself. [7] 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.[8] The loss of these two genes resulted in death of the embryo 9.5 days after conception.[8] It was found that the developing hearts of these embryos lacked most structural formations which resulted in massive hemorrhage.[8] 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.[8]

Clinical significance[edit]

Common variants of SCN5A, SCN10A, and HEY2 (this gene) are associated with Brugada syndrome.[9]

Interactions[edit]

HEY2 has been shown to interact with Sirtuin 1[10] and Nuclear receptor co-repressor 1.[11]

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000135547 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000019789 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:".
  4. ^ "Mouse PubMed Reference:".
  5. ^ Leimeister C, Externbrink A, Klamt B, Gessler M (July 1999). "Hey genes: a novel subfamily of hairy- and Enhancer of split related genes specifically expressed during mouse embryogenesis". Mechanisms of Development. 85 (1–2): 173–7. doi:10.1016/S0925-4773(99)00080-5. PMID 10415358.
  6. ^ a b "Entrez Gene: HEY2 hairy/enhancer-of-split related with YRPW motif 2".
  7. ^ a b c Gibb N, Lazic S, Yuan X, Deshwar AR, Leslie M, Wilson MD, Scott IC (November 2018). "Hey2 regulates the size of the cardiac progenitor pool during vertebrate heart development". Development. 145 (22): dev167510. doi:10.1242/dev.167510. PMID 30355727.
  8. ^ a b c d Fischer A, Schumacher N, Maier M, Sendtner M, Gessler M (April 2004). "The Notch target genes Hey1 and Hey2 are required for embryonic vascular development". Genes & Development. 18 (8): 901–11. doi:10.1101/gad.291004. PMC 395849. PMID 15107403.
  9. ^ Bezzina CR, Barc J, Mizusawa Y, Remme CA, Gourraud JB, Simonet F, et al. (September 2013). "Common variants at SCN5A-SCN10A and HEY2 are associated with Brugada syndrome, a rare disease with high risk of sudden cardiac death". Nature Genetics. 45 (9): 1044–9. doi:10.1038/ng.2712. PMC 3869788. PMID 23872634.
  10. ^ Takata T, Ishikawa F (January 2003). "Human Sir2-related protein SIRT1 associates with the bHLH repressors HES1 and HEY2 and is involved in HES1- and HEY2-mediated transcriptional repression". Biochemical and Biophysical Research Communications. 301 (1): 250–7. doi:10.1016/S0006-291X(02)03020-6. PMID 12535671.
  11. ^ Iso T, Sartorelli V, Poizat C, Iezzi S, Wu HY, Chung G, et al. (September 2001). "HERP, a novel heterodimer partner of HES/E(spl) in Notch signaling". Molecular and Cellular Biology. 21 (17): 6080–9. doi:10.1128/MCB.21.17.6080-6089.2001. PMC 87325. PMID 11486045.

Further reading[edit]

External links[edit]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.