TY - JOUR
T1 - An early Myc-dependent transcriptional program orchestrates cell growth during B-cell activation
AU - Tesi, Alessandra
AU - de Pretis, Stefano
AU - Furlan, Mattia
AU - Filipuzzi, Marco
AU - Morelli, Marco J.
AU - Andronache, Adrian
AU - Doni, Mirko
AU - Verrecchia, Alessandro
AU - Pelizzola, Mattia
AU - Amati, Bruno
AU - Sabò, Arianna
PY - 2019/9/1
Y1 - 2019/9/1
N2 - 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.
AB - 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.
KW - B-cell
KW - Myc
KW - transcription
UR - http://www.scopus.com/inward/record.url?scp=85069922884&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85069922884&partnerID=8YFLogxK
U2 - 10.15252/embr.201947987
DO - 10.15252/embr.201947987
M3 - Article
C2 - 31334602
AN - SCOPUS:85069922884
VL - 20
JO - EMBO Reports
JF - EMBO Reports
SN - 1469-221X
IS - 9
M1 - e47987
ER -