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Status |
Public on May 01, 2017 |
Title |
Chromatin interactions involving super-enhancers associate with specific expression patterns of target genes |
Organism |
Homo sapiens |
Experiment type |
Other
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Summary |
Super-enhancers may regulate target genes through chromatin looping. We connected super-enhancers in the K562 chronic myelogenous leukemia cell line with chromatin interactions identified from Chromatin Interaction Analysis with Paired-End Tag (ChIA-PET) data. Gene expression at proximal elements that are connected with distal super-enhancers showed significantly higher cell-type specificity than at proximal elements connected with other elements or not involved in interaction. 4C and Episwitch analysis of chromatin interactions showed that certain chromatin interactions are cell-specific, but others are more general. While super-enhancers upstream of c-MYC at the MYC-335 element can be found in other cancers, only super-enhancers downstream of c-MYC can be found in K562. 4C analysis of the c-MYC promoter revealed no chromatin interactions that are directed upstream of c-MYC, but only downstream of c-MYC, in the PVT1 long non-coding RNA gene. Cell-specific usage of super-enhancers could explain why the MYC-335 element that is associated with many solid cancers such as colorectal cancer and breast cancer, but not with leukemia. Surprisingly, we found that a chromatin interaction between c-MYC and a c-MYC super-enhancer is lost in chronic myelogenous leukemia patient blood as compared with blood from individuals without the disease through Oxford Biodynamics’ Episwitch analysis. These results provide evidence for fine-tuning of expression patterns, such as cell-specific regulation of target genes by distal super-enhancers through chromatin interactions and an association between chromatin interactions and disease, and highlight that super-enhancers are more complex than previously described.
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Overall design |
Examination of several chromatin interactions involving super-enhancers using 4C-Seq and Episwitch (TM)
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Contributor(s) |
Tan HK, Cao F, Fullwood M |
Citation(s) |
28526829 |
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Submission date |
Jan 22, 2016 |
Last update date |
May 15, 2019 |
Contact name |
Melissa Jane Fullwood |
E-mail(s) |
mfullwood@ntu.edu.sg
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Organization name |
Nanyang Technological University
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Department |
School of Biological Sciences
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Lab |
Fullwood lab
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Street address |
14 Medical Drive, #12-01
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City |
Singapore |
ZIP/Postal code |
117599 |
Country |
Singapore |
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Platforms (1) |
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Samples (6)
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Relations |
BioProject |
PRJNA309504 |
SRA |
SRP068767 |