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CTCF-mediated functional chromatin interactome in pluripotent cells.
Lusy Handoko1, Han Xu, Guoliang Li
1Genome Institute of Singapore, Singapore.
Nature Genetics
|June 21, 2011
Summary
This study maps the CTCF-chromatin interactome in pluripotent cells using ChIA-PET sequencing. Findings reveal CTCF
Area of Science:
- Genomics and Molecular Biology
- Cellular and Developmental Biology
Background:
- Mammalian genomes are organized to regulate gene expression spatially and temporally.
- CTCF (CCCTC-binding factor) is a key protein involved in genome organization.
- Global CTCF-associated higher-order chromatin structures remain largely uncharacterized.
Purpose of the Study:
- To elucidate the CTCF-chromatin interactome in pluripotent cells using ChIA-PET.
- To identify global CTCF-associated higher-order chromatin structures.
- To explore the functional implications of CTCF interactions in genome organization and gene regulation.
Main Methods:
- Chromatin interaction analysis by paired-end tag (ChIA-PET) sequencing was applied.
- Identification of cis- and trans-interacting CTCF loci with high reproducibility.
- Integration of interaction data with epigenetic states, promoter activity, enhancer binding, and nuclear lamina occupancy.
Main Results:
- 1,480 cis- and 336 trans-interacting CTCF loci were identified.
- Five distinct chromatin domains associated with CTCF interactions were uncovered.
- CTCF interactions were found to demarcate chromatin-nuclear membrane attachments.
- CTCF interactions influence gene expression via cross-talk between promoters and regulatory elements.
Conclusions:
- CTCF plays a crucial role in organizing higher-order chromatin structures in pluripotent cells.
- CTCF interactions are linked to nuclear lamina attachment and gene expression regulation.
- These findings propose new models for CTCF function in chromatin organization and transcriptional control.
- The study provides insights into the principles governing genome plasticity and function.
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