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Stochastic Gene Choice during Cellular Differentiation.

Takeo Wada1, Sandrine Wallerich1, Attila Becskei1

  • 1Biozentrum, University of Basel, Klingelbergstrasse 50/70, Basel 4056, Switzerland.

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|September 27, 2018
PubMed
Summary

Gene expression in higher eukaryotes involves complex interactions. This study quantifies gene interdependence during neuronal differentiation, revealing a shift from co-occurrence to exclusivity in the protocadherin cluster.

Keywords:
CTCFCpG methylationcell fate determinationembryonic stem cellenhancerepigeneticgene expression noiseneuronal diversityneuronal progenitorpromoter

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Area of Science:

  • Genetics
  • Developmental Biology
  • Neuroscience

Background:

  • Gene expression regulation in eukaryotes involves long-range interactions.
  • These interactions determine gene co-occurrence, independence, or exclusivity within chromosomal segments.
  • The protocadherin (Pcdh) cluster is crucial for neuronal diversity and exhibits complex expression patterns.

Purpose of the Study:

  • To introduce a quantitative measure for gene expression interdependence.
  • To investigate the dynamics of gene isoform expression within the Pcdh cluster during neuronal differentiation.
  • To understand the relationship between gene expression patterns and CTCF binding during differentiation.

Main Methods:

  • Developed a novel measure to quantify gene expression interdependence.
  • Differentiated mouse embryonic stem cells into neurons.
  • Measured single-cell gene isoform expression in the Pcdh cluster.
  • Correlated gene expression frequency with CTCF binding dynamics.

Main Results:

  • Pcdh gene isoform expression shifts from concurrent to exclusive during neuronal differentiation.
  • Increasing differentiation leads to a greater degree of expression exclusivity.
  • Gene expression frequency strongly correlates with CTCF binding to promoters.
  • CTCF binding dynamics dynamically influence Pcdh gene expression patterns.

Conclusions:

  • Cellular differentiation involves stochastic gene choice, particularly evident in the Pcdh cluster.
  • CTCF binding plays a critical role in regulating Pcdh gene expression dynamics.
  • The findings provide insights into the interplay between differentiation and gene regulation.