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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.
Abstract:
During cell division, transcription factors (TFs) are removed from chromatin twice, during DNA synthesis and during condensation of chromosomes. How TFs can efficiently find their sites following these stages has been unclear. Here, we have analyzed the binding pattern of expressed TFs in human colorectal cancer cells. We find that binding of TFs is highly clustered and that the clusters are enriched in binding motifs for several major TF classes. Strikingly, almost all clusters are formed around cohesin, and loss of cohesin decreases both DNA accessibility and binding of TFs to clusters. We show that cohesin remains bound in S phase, holding the nascent sister chromatids together at the TF cluster sites. Furthermore, cohesin remains bound to the cluster sites when TFs are evicted in early M phase. These results suggest that cohesin-binding functions as a cellular memory that promotes re-establishment of TF clusters after DNA replication and chromatin condensation.
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.
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