An early Myc-dependent transcriptional program orchestrates cell growth during B-cell activation.
Animals
B-Lymphocytes
/ metabolism
Cell Cycle
/ genetics
Cell Proliferation
/ genetics
Chromatin Immunoprecipitation
Female
Gene Expression Regulation, Neoplastic
/ genetics
High-Throughput Nucleotide Sequencing
Immunoblotting
Male
Mice
Mice, Inbred C57BL
Promoter Regions, Genetic
/ genetics
Proto-Oncogene Proteins c-myc
/ genetics
RNA Polymerase II
/ genetics
Transcription, Genetic
/ genetics
B-cell
Myc
transcription
Journal
EMBO reports
ISSN: 1469-3178
Titre abrégé: EMBO Rep
Pays: England
ID NLM: 100963049
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
24
02
2019
revised:
18
06
2019
accepted:
27
06
2019
pubmed:
25
7
2019
medline:
2
6
2020
entrez:
24
7
2019
Statut:
ppublish
Résumé
Upon activation, lymphocytes exit quiescence and undergo substantial increases in cell size, accompanied by activation of energy-producing and anabolic pathways, widespread chromatin decompaction, and elevated transcriptional activity. These changes depend upon prior induction of the Myc transcription factor, but how Myc controls them remains unclear. We addressed this issue by profiling the response to LPS stimulation in wild-type and c-myc-deleted primary mouse B-cells. Myc is rapidly induced, becomes detectable on virtually all active promoters and enhancers, but has no direct impact on global transcriptional activity. Instead, Myc contributes to the swift up- and down-regulation of several hundred genes, including many known regulators of the aforementioned cellular processes. Myc-activated promoters are enriched for E-box consensus motifs, bind Myc at the highest levels, and show enhanced RNA Polymerase II recruitment, the opposite being true at down-regulated loci. Remarkably, the Myc-dependent signature identified in activated B-cells is also enriched in Myc-driven B-cell lymphomas: hence, besides modulation of new cancer-specific programs, the oncogenic action of Myc may largely rely on sustained deregulation of its normal physiological targets.
Identifiants
pubmed: 31334602
doi: 10.15252/embr.201947987
pmc: PMC6726900
mid: EMS83630
doi:
Substances chimiques
Proto-Oncogene Proteins c-myc
0
RNA Polymerase II
EC 2.7.7.-
Banques de données
GEO
['GSE126340']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e47987Subventions
Organisme : European Research Council
ID : 268671
Pays : International
Organisme : Worldwide Cancer Research
ID : 15-1260
Pays : United Kingdom
Organisme : EC|FP7|FP7 Ideas: European Research Council (FP7 Ideas)
ID : 268671-MYCNEXT
Pays : International
Organisme : Associazione Italiana per la Ricerca sul Cancro (AIRC)
ID : 2012-13182
Pays : International
Organisme : Ministero della Salute (Ministry of Health, Italy)
ID : RF-2011-02346976
Pays : International
Organisme : Associazione Italiana per la Ricerca sul Cancro (AIRC)
ID : 2015-16768
Pays : International
Informations de copyright
© 2019 The Authors.
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