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Master Transcription Regulators02:23

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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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Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome.  Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form...
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Transcriptional Regulation: Riboswitches01:23

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Riboswitches are RNA elements that regulate gene expression by altering their secondary structures in response to specific effector molecules. These elements, located in the leader regions of certain mRNAs, act as transcriptional regulators by toggling between alternative conformations to control downstream gene expression. Riboswitch-mediated regulation is a precise mechanism for modulating biosynthetic pathways, as exemplified by the riboflavin biosynthesis pathway in Bacillus...
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Transcription Factors02:16

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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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Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome
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Dppa2 and Dppa4 directly regulate the Dux-driven zygotic transcriptional program.

Mélanie Eckersley-Maslin1, Celia Alda-Catalinas1, Marloes Blotenburg1

  • 1Epigenetics Programme, Babraham Institute, Cambridge CB22 3AT, United Kingdom.

Genes & Development
|January 30, 2019
PubMed
Summary

Developmental pluripotency-associated 2 (Dppa2) and Dppa4 initiate zygotic genome activation (ZGA) by upregulating Dux. This establishes the 2C-like cell state, which is then stabilized by Zscan4c.

Keywords:
2C-like cellsDNA methylationDppa2Dppa4DuxZscan4embryonic stem cellepigeneticzygotic genome activation

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Area of Science:

  • * Developmental Biology
  • * Epigenetics
  • * Stem Cell Biology

Background:

  • * Mammalian zygotic genome activation (ZGA) is crucial for early development.
  • * 2C-like cells in mouse embryonic stem cells model ZGA transcription.
  • * The transcription factor Dux is known to activate ZGA genes.

Purpose of the Study:

  • * Identify upstream maternal factors regulating ZGA.
  • * Investigate the role of Dppa2 and Dppa4 in ZGA.
  • * Elucidate the molecular hierarchy of 2C-like transcriptional program initiation and stabilization.

Main Methods:

  • * Candidate-based overexpression screen.
  • * Overexpression, knockdown, knockout, and rescue experiments.
  • * Transcriptional analyses and ChIP-seq (chromatin immunoprecipitation followed by sequencing).

Main Results:

  • * Dppa2 and Dppa4 promote 2C-like cells and ZGA gene transcription.
  • * Dppa2 and Dppa4 bind to the Dux promoter and drive its expression, initiating the 2C-like program.
  • * Zscan4c stabilizes the 2C-like transcriptional network but does not initiate it.

Conclusions:

  • * Dppa2 and Dppa4 act upstream of Dux to initiate ZGA.
  • * A molecular hierarchy exists where Dppa2/4 drive Dux expression, leading to the 2C-like state.
  • * Zscan4c reinforces the Dppa2/4-Dux-mediated transcriptional program.