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Gene Review

HEY1  -  hes-related family bHLH transcription...

Homo sapiens

Synonyms: BHLHB31, BHLHb31, CHF-2, CHF2, Cardiovascular helix-loop-helix factor 2, ...
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Disease relevance of HEY1


Psychiatry related information on HEY1


High impact information on HEY1


Biological context of HEY1


Anatomical context of HEY1

  • In a luciferase reporter system, RTA activated the hey1 promoter in several cell lines; conversely, HEY1 repressed the rta promoter [1].
  • After induction of myotube formation in low serum, CHF2 expression is barely detectable at 3 days after induction [10].
  • In undifferentiated myoblasts, CHF2 is expressed at high levels [10].
  • Analysis of embryonic murine hesr-1 expression by in situ hybridization reveals strong expression in the somitic mesoderm, the central nervous system, the kidney, the heart, nasal epithelium, and limbs indicating a role for hesr-1 in the development of these tissues [12].
  • HESR1 is necessary for the induction of a tubular network and for continued maintenance of mature and quiescent blood vessels [2].

Associations of HEY1 with chemical compounds

  • While the overall structure with the bHLH domain, Orange domain, and WRPW motif is similar, the last motif is changed to KPYRPWG in Hey1/2 and absent in HeyL [8].
  • These results suggest that Hesr1 and its polymorphism(s) might be involved in dopamine-related polygenic disorders and behavioral traits [13].
  • METHODS: A total of 321 postmenopausal women were randomized to 1 mg 17beta-estradiol plus 0.025 mg gestodene for 12 days every month (HRT 1), or 1 mg 17beta-estradiol plus 0.025 mg gestodene for 12 days every third month (HRT 2), or no-HRT, during 48 weeks [14].
  • In general, the sulfonamide analogues with a CHF2 at C-3 were found to be more potent than those having a CF3 group [15].
  • Among the subjects with the usual phenotype, the CHF2 C5- phenotype was more frequent in the mildly poisoned group (94.3%) than in the control group (81.0%), leading to an RR of 3.9 when compared to the CHE2 C5+ phenotype [16].

Regulatory relationships of HEY1

  • Thus, HESR1 represses VEGFR2 through interactions with SP-1-like factors and requires an Inr element in the absence of a TATA box [17].
  • HESR1 seems to inhibit the vessel-promoting effects of VEGF, shift endothelial cells from a proliferative state to a quiescent state, and restore normal vessel structures [2].

Other interactions of HEY1

  • We have isolated and characterized three new hairy-related bHLH transcription factor genes from mouse and human (hairy and Enhancer-of-split related with YRPW motif; HEY1, HEY2, and HEYL) [8].
  • Importantly, HERP2 is an immediate target gene of Notch signaling since HERP2 mRNA expression is induced even in the absence of de novo protein synthesis [18].
  • The VEGFR2 promoter contains a functional initiator element but no TATA box, however, addition of a TATA sequence renders the promoter resistant to inhibition by HESR1 [17].
  • Which co-repressors are required in vivo for AR repression by anti-androgens is not clear, but one candidate is the Notch effector Hey1 [19].

Analytical, diagnostic and therapeutic context of HEY1

  • We assessed the risk of breast cancer associated with HRT use in 54,548 postmenopausal women who had never taken any HRT 1 year before entering the E3N-EPIC cohort study (mean age at inclusion: 52.8 years); 948 primary invasive breast cancers were diagnosed during follow-up (mean duration: 5.8 years) [20].
  • To investigate functions of the HESR1 gene in the dopaminergic nervous system in vivo, we analyzed the expressions of dopamine-related genes in the postnatal day 0 whole brains of Hesr1 knockout mice by real-time RT-PCR analysis [5].
  • Using DNA chip technology, we showed that hey1, a basic helix-loop-helix-containing transcription factor, increased three- to fourfold in this line [1].
  • Two distinct PCR fragments, chf1 and chf2, were isolated and used to identify two DNA contigs [21].


  1. KSHV RTA induces a transcriptional repressor, HEY1 that represses rta promoter. Yada, K., Do, E., Sakakibara, S., Ohsaki, E., Ito, E., Watanabe, S., Ueda, K. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  2. Protective effects of transcription factor HESR1 on retinal vasculature. Li, B., Tang, S.B., Hu, J., Gao, Y., Zhang, G., Lin, S.F., Chen, J.H., Li, B.J. Microvasc. Res. (2006) [Pubmed]
  3. Combined loss of Hey1 and HeyL causes congenital heart defects because of impaired epithelial to mesenchymal transition. Fischer, A., Steidl, C., Wagner, T.U., Lang, E., Jakob, P.M., Friedl, P., Knobeloch, K.P., Gessler, M. Circ. Res. (2007) [Pubmed]
  4. Hey1, a mediator of notch signaling, is an androgen receptor corepressor. Belandia, B., Powell, S.M., García-Pedrero, J.M., Walker, M.M., Bevan, C.L., Parker, M.G. Mol. Cell. Biol. (2005) [Pubmed]
  5. Hesr1 knockout mice exhibit behavioral alterations through the dopaminergic nervous system. Fuke, S., Minami, N., Kokubo, H., Yoshikawa, A., Yasumatsu, H., Sasagawa, N., Saga, Y., Tsukahara, T., Ishiura, S. J. Neurosci. Res. (2006) [Pubmed]
  6. Hey basic helix-loop-helix transcription factors are repressors of GATA4 and GATA6 and restrict expression of the GATA target gene ANF in fetal hearts. Fischer, A., Klattig, J., Kneitz, B., Diez, H., Maier, M., Holtmann, B., Englert, C., Gessler, M. Mol. Cell. Biol. (2005) [Pubmed]
  7. Jun blockade of erythropoiesis: role for repression of GATA-1 by HERP2. Elagib, K.E., Xiao, M., Hussaini, I.M., Delehanty, L.L., Palmer, L.A., Racke, F.K., Birrer, M.J., Shanmugasundaram, G., McDevitt, M.A., Goldfarb, A.N. Mol. Cell. Biol. (2004) [Pubmed]
  8. Characterization of the human and mouse HEY1, HEY2, and HEYL genes: cloning, mapping, and mutation screening of a new bHLH gene family. Steidl, C., Leimeister, C., Klamt, B., Maier, M., Nanda, I., Dixon, M., Clarke, R., Schmid, M., Gessler, M. Genomics (2000) [Pubmed]
  9. Up-regulation of delta-like 4 ligand in human tumor vasculature and the role of basal expression in endothelial cell function. Patel, N.S., Li, J.L., Generali, D., Poulsom, R., Cranston, D.W., Harris, A.L. Cancer Res. (2005) [Pubmed]
  10. Regulation of myogenic terminal differentiation by the hairy-related transcription factor CHF2. Sun, J., Kamei, C.N., Layne, M.D., Jain, M.K., Liao, J.K., Lee, M.E., Chin, M.T. J. Biol. Chem. (2001) [Pubmed]
  11. A novel mechanism of transcriptional repression of p27(kip1) through Notch/HRT2 signaling in vascular smooth muscle cells. Havrda, M.C., Johnson, M.J., O'neill, C.F., Liaw, L. Thromb. Haemost. (2006) [Pubmed]
  12. Identification and expression of a novel family of bHLH cDNAs related to Drosophila hairy and enhancer of split. Kokubo, H., Lun, Y., Johnson, R.L. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  13. Identification and characterization of the Hesr1/Hey1 as a candidate trans-acting factor on gene expression through the 3' non-coding polymorphic region of the human dopamine transporter (DAT1) gene. Fuke, S., Sasagawa, N., Ishiura, S. J. Biochem. (2005) [Pubmed]
  14. Hormone replacement therapy and distensibility of carotid arteries in postmenopausal women: a randomized, controlled trial. Angerer, P., Kothny, W., Störk, S., von Schacky, C. J. Am. Coll. Cardiol. (2000) [Pubmed]
  15. Synthesis and SAR/3D-QSAR studies on the COX-2 inhibitory activity of 1,5-diarylpyrazoles to validate the modified pharmacophore. Singh, S.K., Saibaba, V., Rao, K.S., Reddy, P.G., Daga, P.R., Rajjak, S.A., Misra, P., Rao, Y.K. European journal of medicinal chemistry. (2005) [Pubmed]
  16. Butyrylcholinesterase variants (BCHE and CHE2 Loci) associated with erythrocyte acetylcholinesterase inhibition in farmers exposed to pesticides. Fontoura-da-Silva, S.E., Chautard-Freire-Maia, E.A. Hum. Hered. (1996) [Pubmed]
  17. HESR1/CHF2 suppresses VEGFR2 transcription independent of binding to E-boxes. Holderfield, M.T., Henderson Anderson, A.M., Kokubo, H., Chin, M.T., Johnson, R.L., Hughes, C.C. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  18. HERP, a new primary target of Notch regulated by ligand binding. Iso, T., Sartorelli, V., Chung, G., Shichinohe, T., Kedes, L., Hamamori, Y. Mol. Cell. Biol. (2001) [Pubmed]
  19. Mechanisms of androgen receptor repression in prostate cancer. Powell, S.M., Brooke, G.N., Whitaker, H.C., Reebye, V., Gamble, S.C., Chotai, D., Dart, D.A., Belandia, B., Bevan, C.L. Biochem. Soc. Trans. (2006) [Pubmed]
  20. Breast cancer risk in relation to different types of hormone replacement therapy in the E3N-EPIC cohort. Fournier, A., Berrino, F., Riboli, E., Avenel, V., Clavel-Chapelon, F. Int. J. Cancer (2005) [Pubmed]
  21. Isolation and characterization of chitinases from Verticillium lecanii. Lu, Z.X., Laroche, A., Huang, H.C. Can. J. Microbiol. (2005) [Pubmed]
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