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Status |
Public on Aug 08, 2023 |
Title |
Multi-scale epigenomic priming of inflammatory genes enables rapid recall in human memory T helper cells [ChIP-seq] |
Organism |
Homo sapiens |
Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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Summary |
Memory T cells provide long-lasting defense responses through their ability to rapidly reactivate. How memory T cells efficiently ‘recall’ an inflammatory transcriptional program remains unclear. Here, we show that primary human CD4+ memory T helper (Th) cells carry three distinct activation-inducible recall gene modules that drive metabolic adaptation, T cell activation and inflammatory cytokine production. Enhancer elements controlling recall genes were epigenetically primed through the local maintenance of transcription-permissive chromatin in resting memory Th cells. At the three-dimensional level, recall genes clustered in transcriptionally permissive subnuclear compartments and resided in topologically associating domains (‘memory TADs’), in which activation-associated promoter-enhancer interactions were pre-formed. This primed epigenomic landscape was exploited by AP-1 transcription factors - including MAF - to promote rapid transcriptional activation. Finally, recall genes and their enhancers were linked to memory Th cell dysfunction in chronic inflammatory disease. Together, our results implicate multi-scale epigenomic priming - comprising a specialized three-dimensional chromatin organization - as a key mechanism underlying immunological memory.
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Overall design |
ChIP-Seq (n=2-3 biological replicates, independent donors) was performed on primary human naive or memory T helper cells.
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Contributor(s) |
van Schoonhoven A, Stadhouders R |
Citation(s) |
37418545 |
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Submission date |
Aug 11, 2022 |
Last update date |
Aug 09, 2023 |
Contact name |
Ralph Stadhouders |
E-mail(s) |
stadhoudersralph@gmail.com
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Organization name |
Erasmus Medical Center
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Department |
Pulmonary Medicine
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Street address |
Dr. Molewaterplein 50
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City |
Rotterdam |
ZIP/Postal code |
3015 GE |
Country |
Netherlands |
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Platforms (1) |
GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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Samples (11)
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GSM6447499 |
H3K4me2 naive CD4+ T cell, resting (rep1) |
GSM6447500 |
H3K4me2 naive CD4+ T cell, resting (rep2) |
GSM6447501 |
H3K4me2 naive CD4+ T cell, resting (rep3) |
GSM6447502 |
H3K4me2 memory Th1 CD4+ T cell, resting (rep1) |
GSM6447503 |
H3K4me2 memory Th1 CD4+ T cell, resting (rep2) |
GSM6447504 |
H3K4me2 memory Th17 CD4+ T cell, resting (rep1) |
GSM6447505 |
H3K4me2 memory Th17 CD4+ T cell, resting (rep2) |
GSM6447506 |
H3K4me2 memory Th17 CD4+ T cell, resting (rep3) |
GSM6447507 |
H3K4me2 memory Th2 CD4+ T cell, resting (rep1) |
GSM6447508 |
H3K4me2 memory Th2 CD4+ T cell, resting (rep2) |
GSM6447509 |
H3K4me2 memory Th2 CD4+ T cell, resting (rep3) |
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This SubSeries is part of SuperSeries: |
GSE211389 |
Multi-scale epigenomic priming of inflammatory genes enables rapid recall in human memory T helper cells |
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Relations |
BioProject |
PRJNA868704 |