TT‐seq captures enhancer landscapes immediately after T‐cell stimulation

Abstract To monitor transcriptional regulation in human cells, rapid changes in enhancer and promoter activity must be captured with high sensitivity and temporal resolution. Here, we show that the recently established protocol TT‐seq (“transient transcriptome sequencing”) can monitor rapid changes...

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Main Authors: Margaux Michel, Carina Demel, Benedikt Zacher, Björn Schwalb, Stefan Krebs, Helmut Blum, Julien Gagneur, Patrick Cramer
Format: Article
Language:English
Published: Springer Nature 2017-03-01
Series:Molecular Systems Biology
Subjects:
Online Access:https://doi.org/10.15252/msb.20167507
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author Margaux Michel
Carina Demel
Benedikt Zacher
Björn Schwalb
Stefan Krebs
Helmut Blum
Julien Gagneur
Patrick Cramer
author_facet Margaux Michel
Carina Demel
Benedikt Zacher
Björn Schwalb
Stefan Krebs
Helmut Blum
Julien Gagneur
Patrick Cramer
author_sort Margaux Michel
collection DOAJ
description Abstract To monitor transcriptional regulation in human cells, rapid changes in enhancer and promoter activity must be captured with high sensitivity and temporal resolution. Here, we show that the recently established protocol TT‐seq (“transient transcriptome sequencing”) can monitor rapid changes in transcription from enhancers and promoters during the immediate response of T cells to ionomycin and phorbol 12‐myristate 13‐acetate (PMA). TT‐seq maps eRNAs and mRNAs every 5 min after T‐cell stimulation with high sensitivity and identifies many new primary response genes. TT‐seq reveals that the synthesis of 1,601 eRNAs and 650 mRNAs changes significantly within only 15 min after stimulation, when standard RNA‐seq does not detect differentially expressed genes. Transcription of enhancers that are primed for activation by nucleosome depletion can occur immediately and simultaneously with transcription of target gene promoters. Our results indicate that enhancer transcription is a good proxy for enhancer regulatory activity in target gene activation, and establish TT‐seq as a tool for monitoring the dynamics of enhancer landscapes and transcription programs during cellular responses and differentiation.
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spelling doaj.art-d9ba39013dbf4535975a262b784bdd132024-03-03T07:05:19ZengSpringer NatureMolecular Systems Biology1744-42922017-03-01133n/an/a10.15252/msb.20167507TT‐seq captures enhancer landscapes immediately after T‐cell stimulationMargaux Michel0Carina Demel1Benedikt Zacher2Björn Schwalb3Stefan Krebs4Helmut Blum5Julien Gagneur6Patrick Cramer7Department of Molecular Biology Max Planck Institute for Biophysical Chemistry Göttingen GermanyDepartment of Molecular Biology Max Planck Institute for Biophysical Chemistry Göttingen GermanyGene Center Munich Ludwig‐Maximilians‐Universität München Munich GermanyDepartment of Molecular Biology Max Planck Institute for Biophysical Chemistry Göttingen GermanyGene Center Munich Ludwig‐Maximilians‐Universität München Munich GermanyGene Center Munich Ludwig‐Maximilians‐Universität München Munich GermanyDepartment of Informatics Technische Universität München Garching GermanyDepartment of Molecular Biology Max Planck Institute for Biophysical Chemistry Göttingen GermanyAbstract To monitor transcriptional regulation in human cells, rapid changes in enhancer and promoter activity must be captured with high sensitivity and temporal resolution. Here, we show that the recently established protocol TT‐seq (“transient transcriptome sequencing”) can monitor rapid changes in transcription from enhancers and promoters during the immediate response of T cells to ionomycin and phorbol 12‐myristate 13‐acetate (PMA). TT‐seq maps eRNAs and mRNAs every 5 min after T‐cell stimulation with high sensitivity and identifies many new primary response genes. TT‐seq reveals that the synthesis of 1,601 eRNAs and 650 mRNAs changes significantly within only 15 min after stimulation, when standard RNA‐seq does not detect differentially expressed genes. Transcription of enhancers that are primed for activation by nucleosome depletion can occur immediately and simultaneously with transcription of target gene promoters. Our results indicate that enhancer transcription is a good proxy for enhancer regulatory activity in target gene activation, and establish TT‐seq as a tool for monitoring the dynamics of enhancer landscapes and transcription programs during cellular responses and differentiation.https://doi.org/10.15252/msb.20167507enhancersfunctional genomicspromotersT‐cell responsetranscriptome analysis
spellingShingle Margaux Michel
Carina Demel
Benedikt Zacher
Björn Schwalb
Stefan Krebs
Helmut Blum
Julien Gagneur
Patrick Cramer
TT‐seq captures enhancer landscapes immediately after T‐cell stimulation
Molecular Systems Biology
enhancers
functional genomics
promoters
T‐cell response
transcriptome analysis
title TT‐seq captures enhancer landscapes immediately after T‐cell stimulation
title_full TT‐seq captures enhancer landscapes immediately after T‐cell stimulation
title_fullStr TT‐seq captures enhancer landscapes immediately after T‐cell stimulation
title_full_unstemmed TT‐seq captures enhancer landscapes immediately after T‐cell stimulation
title_short TT‐seq captures enhancer landscapes immediately after T‐cell stimulation
title_sort tt seq captures enhancer landscapes immediately after t cell stimulation
topic enhancers
functional genomics
promoters
T‐cell response
transcriptome analysis
url https://doi.org/10.15252/msb.20167507
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