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Related Concept Videos

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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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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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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The Sox2 transcription factor binds RNA.

Zachariah E Holmes1, Desmond J Hamilton1, Taeyoung Hwang1

  • 1Department of Biochemistry, University of Colorado at Boulder, Campus Box 596, Boulder, CO, 80309, USA.

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|April 15, 2020
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Sox2 directly binds RNA with high affinity but low specificity. This study reveals novel direct interactions between Sox2 and RNA in vitro and in vivo, impacting gene regulation.

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Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • Transcription factors regulate gene expression through interactions with DNA and RNA.
  • Sox2 is crucial for pluripotency and neurogenesis, and its association with long non-coding RNAs (lncRNAs) has been observed, but direct interactions are unconfirmed.

Purpose of the Study:

  • To investigate whether Sox2 directly interacts with lncRNAs.
  • To characterize the mechanism and specificity of Sox2-RNA interactions.

Main Methods:

  • In vitro binding assays to assess direct interaction between human Sox2 and lncRNA.
  • UV-cross-linked immunoprecipitation (CLIP) in mouse embryonic stem cells to detect in vivo RNA binding.
  • Fast RNA immunoprecipitation sequencing (fRIP-seq) to identify Sox2-bound RNAs in vivo.

Main Results:

  • Human Sox2 directly binds to a specific lncRNA with high affinity in vitro via its HMG DNA-binding domain.
  • Sox2-RNA interactions are primarily with double-stranded RNA and are non-sequence specific.
  • Over a thousand Sox2-RNA interactions were identified in vivo in mouse embryonic stem cells.

Conclusions:

  • Sox2 directly interacts with RNA through its DNA-binding domain.
  • Sox2 exhibits a high-affinity, low-specificity RNA binding paradigm.
  • These findings reveal a novel mechanism for gene regulation involving direct Sox2-RNA interactions.