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Bhlha15  -  basic helix-loop-helix family, member a15

Mus musculus

Synonyms: 1810009C13Rik, Bhlhb8, Class A basic helix-loop-helix protein 15, Class B basic helix-loop-helix protein 8, MIST-1, ...
 
 
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Disease relevance of Bhlhb8

  • Inhibition of Mist1 homodimer formation induces pancreatic acinar-to-ductal metaplasia [1].
 

High impact information on Bhlhb8

 

Biological context of Bhlhb8

  • We conclude that Mist1 functions as a positive regulator of Cx32 gene expression and, in its absence, acinar cell gap junctions and intercellular communication pathways become disrupted [4].
  • To address this, we have gene targeted KrasG12D into the open reading frame of Mist1, a basic helix-loop-helix transcription factor that is expressed during pancreatic development and required for proper pancreatic acinar organization [5].
  • While Mist1 is not expressed in the endocrine pancreas, the disorganized phenotype of the exocrine component may affect endocrine function [6].
  • Cloning of the murine Mist1 gene and assignment to mouse chromosome band 5G2-5G3 [7].
  • In this study, we isolated the mouse Mist1 gene and established its primary DNA sequence and complete genomic structure [7].
 

Anatomical context of Bhlhb8

  • Sgn1, a novel class B bHLH factor, is specifically expressed in the salivary duct cells, while the acinar cells are characterized by the expression of another class B bHLH factor, Mist1 [8].
  • To identify a mechanistic link between granule targeting and the loss of Mist1 function, intercellular junctions and the expression of Rab3D were assessed [9].
  • Mist1 is necessary for the establishment of granule organization in serous exocrine cells of the gastrointestinal tract [9].
  • In this study, we identify Mist1 as a tissue-restricted Class II bHLH transcription factor expressed in lactating mammary glands [10].
  • Our findings suggest that loss of Mist1 impairs the maintenance of the fully differentiated alveolar state and, for the first time, places Mist1 within the hierarchy of known HLH/bHLH proteins that control mammary epithelial cell development [10].
 

Regulatory relationships of Bhlhb8

  • Additional studies testing Mist1 gene constructs in pancreatic exocrine cells confirmed that Mist1 transcriptionally regulates expression of the Cx32 gene [4].
  • These findings suggest that Mist1-expressing cells represent a permissive compartment for transformation by oncogenic Kras in pancreatic tumorigenesis [5].
 

Other interactions of Bhlhb8

  • Altered Glut-2 accumulation and beta-cell function in mice lacking the exocrine-specific transcription factor, Mist1 [6].
  • Pancreatic acinar cells, serous or seromucous cells of the salivary glands, chief cells of the stomach, and secretory cells of the prostate and seminal vesicle show high levels of Mist1 protein, whereas nonserous exocrine cells, including the mucus-producing cells of the salivary glands, remain Mist1 negative [11].
 

Analytical, diagnostic and therapeutic context of Bhlhb8

  • In order to perform a molecular characterization of this protein, we employed coimmunoprecipitation and bimolecular fluorescence complementation assays, coupled with electrophoretic mobility shift assay studies, to show that Mist1 exists in vivo as a homodimer complex [1].
  • Fluorescence in situ hybridization mapping located the Mist1 gene to the telomere of mouse chromosome 5 at position 5G2-5G3, an area which is syntenic to human chromosome 13q and which contains several additional pancreatic regulatory genes including IPF1 and CDX2 [7].
  • Here, we describe a gene expression analysis of laser capture microdissection purified gastric cell populations that identified the bHLH transcription factor Mist1 as a potential ZC regulatory factor [12].
  • Mist1 null (Mist1(KO)) lactating mammary glands were defective in normal lobuloalveolar organization, exhibiting shedding of cells into the alveolus lumen and premature activation of the signal transducer and activator of transcription 3 signaling pathway [10].
  • In an effort to identify specific cell types that contain the Mist1 protein, antibodies specific for Mist1 were generated and used in Western blot and immunohistochemical assays [11].

References

  1. Inhibition of Mist1 homodimer formation induces pancreatic acinar-to-ductal metaplasia. Zhu, L., Tran, T., Rukstalis, J.M., Sun, P., Damsz, B., Konieczny, S.F. Mol. Cell. Biol. (2004) [Pubmed]
  2. The bHLH transcription factor Mist1 is required to maintain exocrine pancreas cell organization and acinar cell identity. Pin, C.L., Rukstalis, J.M., Johnson, C., Konieczny, S.F. J. Cell Biol. (2001) [Pubmed]
  3. The basic helix-loop-helix transcription factor Mist1 functions as a transcriptional repressor of myoD. Lemercier, C., To, R.Q., Carrasco, R.A., Konieczny, S.F. EMBO J. (1998) [Pubmed]
  4. Exocrine specific expression of Connexin32 is dependent on the basic helix-loop-helix transcription factor Mist1. Rukstalis, J.M., Kowalik, A., Zhu, L., Lidington, D., Pin, C.L., Konieczny, S.F. J. Cell. Sci. (2003) [Pubmed]
  5. Mist1-KrasG12D knock-in mice develop mixed differentiation metastatic exocrine pancreatic carcinoma and hepatocellular carcinoma. Tuveson, D.A., Zhu, L., Gopinathan, A., Willis, N.A., Kachatrian, L., Grochow, R., Pin, C.L., Mitin, N.Y., Taparowsky, E.J., Gimotty, P.A., Hruban, R.H., Jacks, T., Konieczny, S.F. Cancer Res. (2006) [Pubmed]
  6. Altered Glut-2 accumulation and beta-cell function in mice lacking the exocrine-specific transcription factor, Mist1. Fazio, E.N., Everest, M., Colman, R., Wang, R., Pin, C.L. J. Endocrinol. (2005) [Pubmed]
  7. Cloning of the murine Mist1 gene and assignment to mouse chromosome band 5G2-5G3. Pin, C.L., Lemercier, C., Konieczny, S.F. Cytogenet. Cell Genet. (1999) [Pubmed]
  8. Sgn1, a basic helix-loop-helix transcription factor delineates the salivary gland duct cell lineage in mice. Yoshida, S., Ohbo, K., Takakura, A., Takebayashi, H., Okada, T., Abe, K., Nabeshima, Y. Dev. Biol. (2001) [Pubmed]
  9. Mist1 is necessary for the establishment of granule organization in serous exocrine cells of the gastrointestinal tract. Johnson, C.L., Kowalik, A.S., Rajakumar, N., Pin, C.L. Mech. Dev. (2004) [Pubmed]
  10. Identification of a basic helix-loop-helix transcription factor expressed in mammary gland alveolar cells and required for maintenance of the differentiated state. Zhao, Y., Johansson, C., Tran, T., Bettencourt, R., Itahana, Y., Desprez, P.Y., Konieczny, S.F. Mol. Endocrinol. (2006) [Pubmed]
  11. Mist1 expression is a common link among serous exocrine cells exhibiting regulated exocytosis. Pin, C.L., Bonvissuto, A.C., Konieczny, S.F. Anat. Rec. (2000) [Pubmed]
  12. The maturation of mucus-secreting gastric epithelial progenitors into digestive-enzyme secreting zymogenic cells requires Mist1. Ramsey, V.G., Doherty, J.M., Chen, C.C., Stappenbeck, T.S., Konieczny, S.F., Mills, J.C. Development (2007) [Pubmed]
 
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