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Transcription Factors02:16

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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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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The cell cycle refers to the sequence of events occurring throughout a typical cell’s life. In eukaryotic cells, the somatic cell cycle has two stages: interphase and the mitotic phase. During interphase, the cell grows, performs its basic metabolic functions, copies its DNA, and prepares for mitotic cell division. Then, during mitosis and cytokinesis, the cell divides its nuclear and cytoplasmic materials, respectively. This generates two daughter cells that are identical to the original...
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In contrast to the lytic cycle, phages infecting bacteria via the lysogenic cycle do not immediately kill their host cell. Instead, they combine their genome with the host genome, allowing the bacteria to replicate the phage DNA along with the bacterial genome. The incorporated copy of the phage genome is called the prophage. Some prophages can re-activate and enter the lytic cycle. This often occurs in response to a perturbation, such as DNA damage, but can also transpire in the absence of...
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Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
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Two Distinct E2F Transcriptional Modules Drive Cell Cycles and Differentiation.

Maria C Cuitiño1, Thierry Pécot1, Daokun Sun2

  • 1Department of Biochemistry and Molecular Biology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425, USA.

Cell Reports
|May 28, 2019
PubMed
Summary

This study reveals how E2F proteins control gene expression during the cell cycle in mice. Two E2F modules coordinate gene regulation in cycling and exiting cells, crucial for mammalian development.

Keywords:
E2FE2F-tagged knockin miceFUCCI mouse embryosRNA-seqcell cycleconfocal microscopydeep learningimage analysisimmunostainingtranscription

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Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Genetics

Background:

  • Cell-cycle-dependent mRNA oscillations are vital for cell proliferation.
  • Mechanisms of cell-cycle-regulated transcription require in vivo validation.

Purpose of the Study:

  • To investigate the in vivo mechanisms controlling cell-cycle-dependent gene expression.
  • To elucidate the role of E2F transcription factors in coordinating gene expression during the cell cycle.

Main Methods:

  • Unbiased transcriptomic profiling of sorted cells from FUCCI mouse embryos.
  • Analysis of gene expression in E2F-tagged knockin mice.
  • Tissue imaging and deep-learning tools for spatiotemporal analysis.

Main Results:

  • E2F transcription factors play a central role in cell-cycle-dependent gene expression.
  • Post-transcriptional mechanisms coordinate nuclear accumulation of E2F activators (E2F3A) and repressors (E2F4, E2F8) in vivo.
  • Spatiotemporal expression of E2Fs mapped at single-cell resolution.

Conclusions:

  • Two distinct E2F modules (E2F3A-8-4 and E2F3A-4) regulate gene expression in cycling and exiting cells, respectively.
  • These E2F modules are critical for mammalian development and cell cycle control.