HEY2

HEY2
Identifiers
Aliases	HEY2, CHF1, GRIDLOCK, GRL, HERP1, HESR2, HRT2, bHLHb32, hes related family bHLH transcription factor with YRPW motif 2
External IDs	OMIM: 604674 MGI: 1341884 HomoloGene: 22705 GeneCards: HEY2
Gene location (Human)
Chr.	Chromosome 6 (human)[1]
End	125,761,269 bp[1]
Gene location (Mouse)
Chr.	Chromosome 10 (mouse)[2]
End	30,842,801 bp[2]
RNA expression pattern
	More reference expression data
Gene ontology
Molecular function	• microsatellite binding; • sequence-specific DNA binding; • DNA binding; • protein dimerization activity; • protein homodimerization activity; • GO:0001131, GO:0001151, GO:0001130, GO:0001204 DNA-binding transcription factor activity; • transcription factor binding; • histone deacetylase binding; • GO:0000983 RNA polymerase II general transcription initiation factor activity; • RNA polymerase II activating transcription factor binding; • GO:0001948 protein binding; • protein heterodimerization activity; • GO:0001200, GO:0001133, GO:0001201 DNA-binding transcription factor activity, RNA polymerase II-specific; • RNA polymerase II regulatory region sequence-specific DNA binding; • GO:0001077, GO:0001212, GO:0001213, GO:0001211, GO:0001205 DNA-binding transcription activator activity, RNA polymerase II-specific; • GO:0001078, GO:0001214, GO:0001206 DNA-binding transcription repressor activity, RNA polymerase II-specific; • GO:0001106 transcription corepressor activity; • sequence-specific double-stranded DNA binding;
Cellular component	• cytoplasm; • transcriptional repressor complex; • Sin3 complex; • nucleoplasm; • cell nucleus;
Biological process	• dorsal aorta morphogenesis; • cardiac vascular smooth muscle cell development; • cochlea development; • pattern specification process; • cell fate commitment; • pulmonary valve morphogenesis; • regulation of auditory receptor cell differentiation; • negative regulation of transcription from RNA polymerase II promoter involved in smooth muscle cell differentiation; • regulation of transcription, DNA-templated; • heart trabecula formation; • tricuspid valve morphogenesis; • regulation of vasculogenesis; • pulmonary artery morphogenesis; • cardiac septum morphogenesis; • negative regulation of cardiac vascular smooth muscle cell differentiation; • muscular septum morphogenesis; • ventricular septum morphogenesis; • protein-DNA complex assembly; • cardiac muscle hypertrophy; • outflow tract morphogenesis; • ascending aorta morphogenesis; • cardiac left ventricle morphogenesis; • labyrinthine layer blood vessel development; • negative regulation of transcription from RNA polymerase II promoter; • coronary vasculature morphogenesis; • smooth muscle cell differentiation; • negative regulation of gene expression; • endocardial cushion to mesenchymal transition involved in heart valve formation; • transcription, DNA-templated; • ventricular trabecula myocardium morphogenesis; • positive regulation of heart rate; • vasculogenesis; • multicellular organism development; • atrial septum morphogenesis; • negative regulation of cardiac muscle cell apoptotic process; • heart development; • arterial endothelial cell differentiation; • positive regulation of cardiac muscle cell proliferation; • blood vessel development; • cardiac muscle hypertrophy in response to stress; • umbilical cord morphogenesis; • negative regulation of transcription regulatory region DNA binding; • mesenchymal cell development; • artery development; • regulation of gene expression; • negative regulation of transcription by transcription factor localization; • negative regulation of transcription initiation from RNA polymerase II promoter; • vascular smooth muscle cell development; • anterior/posterior axis specification; • tricuspid valve formation; • negative regulation of transcription, DNA-templated; • cardiac ventricle morphogenesis; • cardiac right ventricle morphogenesis; • ventricular cardiac muscle cell development; • atrioventricular valve development; • positive regulation of transcription from RNA polymerase II promoter; • negative regulation of Notch signaling pathway; • cardiac epithelial to mesenchymal transition; • Notch signaling involved in heart development; • Notch signaling pathway; • positive regulation of transcription, DNA-templated; • cell differentiation; • regulation of neurogenesis; • aortic valve morphogenesis; • epithelial to mesenchymal transition involved in endocardial cushion formation; • positive regulation of gene expression; • negative regulation of biomineral tissue development; • anterior/posterior pattern specification; • circulatory system development;
	Sources:Amigo / QuickGO
Orthologs
	23493
	15214
	ENSG00000135547
	ENSMUSG00000019789
	Q9UBP5; Q5TF93
	Q9QUS4
	NM_012259
	NM_013904
	NP_036391
	NP_038932
	Wikidata
View/Edit Human	View/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

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

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

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

Interactions

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

References

GRCh38: Ensembl release 89: ENSG00000135547 - Ensembl, May 2017
GRCm38: Ensembl release 89: ENSMUSG00000019789 - Ensembl, May 2017
"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
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. S2CID 17342136.
"Entrez Gene: HEY2 hairy/enhancer-of-split related with YRPW motif 2".
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.
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.
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.
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.
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.

External links

HEY2+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)

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

This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000135547 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000019789 - Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid10415358-5] 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. S2CID 17342136.

[entrez-6] "Entrez Gene: HEY2 hairy/enhancer-of-split related with YRPW motif 2".

[emily1-7] 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.

[emily2-8] 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.

[Bezzina_Barc_2013-9] 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.

[pmid12535671-10] 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.

[pmid11486045-11] 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.