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Related Concept Videos

General Transcription Factors01:30

General Transcription Factors

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...
Master Transcription Regulators02:23

Master Transcription Regulators

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...
Transcription Factors02:16

Transcription Factors

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...
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
Genomic Imprinting and Inheritance02:30

Genomic Imprinting and Inheritance

Diploid organisms inherit genetic material through chromosomes from both parents. Copies of the same gene are known as alleles. In most cases, both alleles are simultaneously expressed and allow various cellular processes to function optimally. If one of the alleles is missing or mutated, the expression of the other allele can compensate; however, this is not true for all genes.
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
RNA Polymerase II Accessory Proteins02:36

RNA Polymerase II Accessory Proteins

Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...

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Related Experiment Video

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Studying Wnt Signaling During Patterning of Conducting Airways
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Studying Wnt Signaling During Patterning of Conducting Airways

Published on: October 16, 2016

Forkhead Box m1 transcription factor is required for perinatal lung function.

Tanya V Kalin1, I-Ching Wang, Lucille Meliton

  • 1Division of Pulmonary Biology, Cincinnati Children's Hospital Research Foundation, 3333 Burnet Avenue, Cincinnati, OH 45229, USA. kal4ti@cchmc.org

Proceedings of the National Academy of Sciences of the United States of America
|November 27, 2008
PubMed
Summary

The transcription factor Foxm1 is crucial for lung maturation and adaptation to air breathing. Its deletion in respiratory cells impairs lung development, leading to respiratory failure in newborn mice.

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Dissection of the Auditory Bulla in Postnatal Mice: Isolation of the Middle Ear Bones and Histological Analysis

Published on: January 4, 2017

Area of Science:

  • Developmental Biology
  • Molecular Biology
  • Respiratory Physiology

Background:

  • Forkhead Box m1 (Foxm1) is a key regulator of DNA replication and mitosis.
  • Global Foxm1 deletion in mice results in embryonic lethality with multi-organ abnormalities.

Purpose of the Study:

  • To investigate the role of Foxm1 in lung development and function.
  • To determine the impact of conditional Foxm1 deletion in respiratory epithelium on lung maturation and air breathing adaptation.

Main Methods:

  • Conditional deletion of Foxm1 in the respiratory epithelium of mice (epFoxm1(-/-)).
  • Analysis of lung growth, branching, proliferation, and maturation.
  • Assessment of gene expression for lung-specific markers (T1-alpha, aquaporin 5, surfactant proteins).
  • In vitro studies of Foxm1 binding and transcriptional activity on surfactant protein promoters.

Main Results:

  • Conditional Foxm1 deletion did not affect lung growth or proliferation but inhibited maturation.
  • epFoxm1(-/-) lungs showed delayed type I cell differentiation and reduced expression of T1-alpha and aquaporin 5.
  • Expression of surfactant proteins A, B, C, and D was decreased.
  • Foxm1 directly activated Sftpb and Sftpa gene promoters in vitro.

Conclusions:

  • Foxm1 is essential for normal lung maturation and surfactant homeostasis.
  • Foxm1 is required for the adaptation to air breathing after birth.
  • Conditional deletion of Foxm1 in respiratory epithelium leads to respiratory failure due to impaired lung maturation.