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Related Concept Videos

Transcription Factors02:16

Transcription Factors

82.7K
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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Transcription Elongation Factors02:35

Transcription Elongation Factors

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Transcription elongation is a dynamic process that alters depending upon the sequence heterogeneity of the DNA being transcribed. Hence, it is not surprising that the elongation complex's composition also varies along the way while transcribing a gene.
The transcription elongation is regulated via pausing of RNA polymerase on several occasions during transcription. In bacteria, these halts are necessary because the transcription of DNA into mRNA is coupled to the translation of that mRNA...
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Transcription Elongation Factors02:35

Transcription Elongation Factors

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General Transcription Factors01:30

General Transcription Factors

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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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Transcription01:10

Transcription

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Overview
Transcription is the process of synthesizing RNA from a DNA sequence by RNA polymerase. It is the first step in producing a protein from a gene sequence. Additionally, many other proteins and regulatory sequences are involved in the proper synthesis of messenger RNA (mRNA). Regulation of transcription is responsible for the differentiation of all the different types of cells and often for the proper cellular response to environmental signals.
Transcription Can Produce Different Kinds...
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Master Transcription Regulators02:23

Master Transcription Regulators

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Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
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A High-content In Vitro Pancreatic Islet β-cell Replication Discovery Platform
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Examining How the MAFB Transcription Factor Affects Islet β-Cell Function Postnatally.

Holly A Cyphert1, Emily M Walker1, Yan Hang1

  • 1Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN.

Diabetes
|November 15, 2018
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Summary

Human islet beta cells differ from mice in MAFB expression. MafB alone cannot fix MafA-deficient beta cells, but it aids maternal beta cell responses during pregnancy.

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Area of Science:

  • Endocrinology
  • Molecular Biology
  • Genetics

Background:

  • Human islet beta cells exhibit sustained MAFB transcription factor expression, unlike in mice.
  • MAFA, another islet beta-cell enriched factor, shows delayed mRNA expression in humans, peaking after age 9.
  • MAFA protein is minimally produced in juvenile human beta cells, and MafB expression is epigenetically silenced postnatally in mice.

Purpose of the Study:

  • To investigate the functional role of MAFB in human islet beta cells.
  • To compare the function of human MAFA/MAFB heterodimers with mouse MafA homodimers.
  • To explore MafB's impact on maternal beta cell adaptation during pregnancy.

Main Methods:

  • Developed a mouse model for ectopic MafB expression in adult beta cells using MafA regulatory elements.
  • Analyzed beta cell function in mice with MafB coexpression and in MafA-deficient mutants.
  • Assessed tryptophan hydroxylase 1 mRNA levels and serotonin biosynthesis in transgenic mice.

Main Results:

  • Coexpression of MafB with MafA in adult mouse beta cells did not cause overt changes, suggesting functional equivalence to mouse MafA homodimers.
  • MafB alone could not rescue beta cell defects in MafA-deficient mice.
  • Transgenic MafB expression elevated tryptophan hydroxylase 1 mRNA during pregnancy, supporting serotonin biosynthesis for maternal beta cell adaptation.

Conclusions:

  • The human adult MAFA/MAFB heterodimer appears functionally similar to the mouse MafA homodimer.
  • MafB plays a distinct role in beta cells, particularly in supporting maternal adaptations during pregnancy via serotonin pathways.
  • These findings offer new insights into MAFB's function in human islet beta cells.