The transition from quiescence to proliferation is a key regulatory step that can be induced by serum stimulation in cultured fibroblasts. The transcription factor Myc is directly induced by serum mitogens and drives a secondary gene expression program that remains largely unknown. Using mRNA profiling, we identify close to 300 Myc-dependent serum response (MDSR) genes, which are induced by serum in a Myc-dependent manner in mouse fibroblasts. Mapping of genomic Myc-binding sites by ChIP-seq technology revealed that most MDSR genes were directly targeted by Myc, but represented a minor fraction (5.5%) of all Myc-bound promoters (which were 22.4% of all promoters). Other target loci were either induced by serum in a Myc-independent manner, were not significantly regulated or were negatively regulated. MDSR gene products were involved in a variety of processes, including nucleotide biosynthesis, ribosome biogenesis, DNA replication and RNA control. Of the 29 MDSR genes targeted by RNA interference, three showed a requirement for cell-cycle entry upon serum stimulation and 11 for long-term proliferation and/or survival. Hence, proper coordination of key regulatory and biosynthetic pathways following mitogenic stimulation relies upon the concerted regulation of multiple Myc-dependent genes. © 2012 Macmillan Publishers Limited All rights reserved.

Genome-wide mapping of Myc binding and gene regulation in serum-stimulated fibroblasts / Perna, D.; Fagà, G.; Verrecchia, A.; Gorski, M. M.; Barozzi, I.; Narang, V.; Khng, J.; Lim, K. C.; Sung, W. -K.; Sanges, R.; Stupka, E.; Oskarsson, T.; Trumpp, A.; Wei, C. -L.; Müller, H.; Amati, B.. - In: ONCOGENE. - ISSN 0950-9232. - 31:13(2012), pp. 1695-1709. [10.1038/onc.2011.359]

Genome-wide mapping of Myc binding and gene regulation in serum-stimulated fibroblasts

Sanges, R.
Membro del Collaboration group
;
2012

Abstract

The transition from quiescence to proliferation is a key regulatory step that can be induced by serum stimulation in cultured fibroblasts. The transcription factor Myc is directly induced by serum mitogens and drives a secondary gene expression program that remains largely unknown. Using mRNA profiling, we identify close to 300 Myc-dependent serum response (MDSR) genes, which are induced by serum in a Myc-dependent manner in mouse fibroblasts. Mapping of genomic Myc-binding sites by ChIP-seq technology revealed that most MDSR genes were directly targeted by Myc, but represented a minor fraction (5.5%) of all Myc-bound promoters (which were 22.4% of all promoters). Other target loci were either induced by serum in a Myc-independent manner, were not significantly regulated or were negatively regulated. MDSR gene products were involved in a variety of processes, including nucleotide biosynthesis, ribosome biogenesis, DNA replication and RNA control. Of the 29 MDSR genes targeted by RNA interference, three showed a requirement for cell-cycle entry upon serum stimulation and 11 for long-term proliferation and/or survival. Hence, proper coordination of key regulatory and biosynthetic pathways following mitogenic stimulation relies upon the concerted regulation of multiple Myc-dependent genes. © 2012 Macmillan Publishers Limited All rights reserved.
31
13
1695
1709
Perna, D.; Fagà, G.; Verrecchia, A.; Gorski, M. M.; Barozzi, I.; Narang, V.; Khng, J.; Lim, K. C.; Sung, W. -K.; Sanges, R.; Stupka, E.; Oskarsson, T.; Trumpp, A.; Wei, C. -L.; Müller, H.; Amati, B.
File in questo prodotto:
File Dimensione Formato  
Perna et al. - 2012 - Genome-wide mapping of Myc binding and gene regula.pdf

non disponibili

Tipologia: Versione Editoriale (PDF)
Licenza: Non specificato
Dimensione 486.98 kB
Formato Adobe PDF
486.98 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/20.500.11767/68494
Citazioni
  • ???jsp.display-item.citation.pmc??? 47
  • Scopus 68
  • ???jsp.display-item.citation.isi??? 67
social impact