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Related Concept Videos

Cell Specific Gene Expression01:58

Cell Specific Gene Expression

Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
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Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
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Single-cell Transcriptomic Analyses of Mouse Pancreatic Endocrine Cells
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Microphthalmia transcription factor regulates pancreatic β-cell function.

Magdalena A Mazur1, Marcus Winkler, Elvira Ganic

  • 1Stem Cell Center, Lund University, Sweden.

Diabetes
|April 24, 2013
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The microphthalmia-associated transcription factor (Mitf) represses pancreatic beta-cell function. Loss of Mitf improves glucose tolerance and insulin secretion by upregulating key genes like Pax6.

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Area of Science:

  • Endocrinology
  • Molecular Biology
  • Genetics

Background:

  • Precise regulation of pancreatic beta-cell function is vital for blood glucose homeostasis.
  • Pax6 is a known regulator of beta-cell specific factors, including insulin and Glut2.
  • Interactions between Pax6 and Mitf have been observed in pigment cell differentiation.

Purpose of the Study:

  • To investigate the role of Mitf in pancreatic beta-cell function and glucose homeostasis.
  • To determine if Mitf influences the expression of key beta-cell regulatory genes.

Main Methods:

  • Analysis of Mitf expression in pancreatic islets during mouse development and in adults.
  • Assessment of glucose tolerance and insulin secretion in Mitf loss-of-function mutant mice.
  • Gene expression analysis (including insulin, Glut2, Pax4, Pax6) in wild-type and mutant islets.
  • Chromatin immunoprecipitation to identify Mitf binding sites.

Main Results:

  • Mitf is expressed in all pancreatic endocrine cells postnatally and in adults.
  • Mitf loss-of-function mutations improved glucose tolerance and enhanced insulin secretion without altering beta-cell mass.
  • Mutant beta-cells showed increased insulin secretion in response to glucose.
  • Transcription of insulin, Glut2, Pax4, and Pax6 was significantly upregulated in Mitf mutant islets.
  • Mitf was shown to bind to regulatory regions of Pax4 and Pax6, repressing their transcription.

Conclusions:

  • Mitf plays a repressive role in regulating pancreatic beta-cell function.
  • Mitf directly regulates Pax6 transcription, which in turn influences insulin and Glut2 expression.
  • Mitf is a novel regulator of beta-cell function and glucose homeostasis.