Transcription factor binding in human cells occurs in dense clusters formed around cohesin anchor sites

Jian Yan1, Martin Enge, Thomas Whitington

  • 1Science for Life Laboratory, Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm 14183, Sweden.

Cell
|August 20, 2013
PubMed

Insights

Transcription factors (TFs) re-bind DNA sites after cell division using cohesin as a cellular memory. Cohesin anchors TF clusters, ensuring accurate gene regulation following DNA replication and chromosome condensation.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • Transcription factors (TFs) are crucial for gene regulation but are removed during cell division.
  • The mechanism by which TFs re-locate to their specific binding sites after DNA replication and chromosome condensation remains poorly understood.

Purpose of the Study:

  • To investigate how transcription factors re-establish binding to chromatin after cell division.
  • To elucidate the role of cohesin in the re-binding of transcription factors.

Main Methods:

  • Analysis of transcription factor binding patterns in human colorectal cancer cells.
  • Investigating the impact of cohesin depletion on DNA accessibility and TF binding.
  • Observing cohesin and TF binding dynamics during S and M phases of the cell cycle.

Main Results:

  • Transcription factor binding is highly clustered on chromatin.
  • These clusters are predominantly located around cohesin.
  • Loss of cohesin reduces DNA accessibility and TF cluster formation.
  • Cohesin remains bound to TF cluster sites during S phase, holding sister chromatids, and persists through M phase after TF eviction.

Conclusions:

  • Cohesin acts as a crucial anchor for transcription factor clusters.
  • Cohesin serves as a cellular memory, facilitating the re-establishment of TF binding sites after DNA replication and chromosome condensation.
  • This mechanism ensures accurate gene regulation continuity throughout the cell cycle.

Related Concept Videos

Transcription Factors02:16

Transcription Factors

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...
Transcription Factors02:16

Transcription Factors

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...
General Transcription Factors01:30

General Transcription Factors

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...
DNA Packaging00:58

DNA Packaging

Overview
Co-activators and Co-repressors02:04

Co-activators and Co-repressors

Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
Co-activators and Co-repressors02:04

Co-activators and Co-repressors

Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...