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Cis-regulatory Sequences02:02

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Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...
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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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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 gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
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Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
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Temporal Ordering of Dynamic Expression Data from Detailed Spatial Expression Maps
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Identification of cis-regulatory modules encoding temporal dynamics during development.

Delphine Potier, Denis Seyres, Céline Guichard

  • 1INSERM, UMR1090 TAGC, Marseille F-13288, France. c.herrmann@dkfz-heidelberg.de.

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Summary
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This study identifies novel cis-regulatory modules and transcription factors controlling gene expression during Drosophila heart development. The findings reveal a modular regulatory system for temporal gene control.

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Area of Science:

  • Developmental Biology
  • Genomics
  • Molecular Biology

Background:

  • Transcriptional regulatory networks orchestrate gene expression during development.
  • Understanding these networks requires knowledge of transcription factors (TFs) and cis-acting DNA elements (CRMs).
  • Current methods often necessitate prior knowledge of involved TFs.

Purpose of the Study:

  • To discover regulatory motifs and CRMs controlling temporal gene expression without prior TF knowledge.
  • To identify potential trans-acting factors regulating gene sets during Drosophila heart development.
  • To investigate the integration of temporal control in developmental gene regulatory networks.

Main Methods:

  • Utilized an in silico approach (cisTargetX) to predict TF binding motifs and CRMs from whole-genome expression dynamics.
  • Focused on adult heart formation in Drosophila.
  • Validated predicted CRMs and motifs in vivo using reporter gene assays.

Main Results:

  • Discovered potential Nuclear Receptor (NR) binding motifs regulating temporal expression profiles of co-expressed genes during Drosophila metamorphosis.
  • Successfully validated predicted CRMs and NR motifs in vivo.
  • Provided evidence for three NRs acting as temporal regulators of target enhancers.

Conclusions:

  • The in silico approach effectively identified CRMs and potential TFs for temporal gene regulation.
  • Results suggest a modular architecture where temporal and spatial gene regulation can be independently encoded by distinct CRMs.