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7 results on '"de Pretis, Stefano"'

1. An early Myc-dependent transcriptional program orchestrates cell growth during B-cell activation

Author

Tesi, A, de Pretis, S, Furlan, M, Filipuzzi, M, Morelli, M, Andronache, A, Doni, M, Verrecchia, A, Pelizzola, M, Amati, B, Sabò, A, Tesi, Alessandra, de Pretis, Stefano, Furlan, Mattia, Filipuzzi, Marco, Morelli, Marco J, Andronache, Adrian, Doni, Mirko, Verrecchia, Alessandro, Pelizzola, Mattia, Amati, Bruno, Sabò, Arianna, Tesi, A, de Pretis, S, Furlan, M, Filipuzzi, M, Morelli, M, Andronache, A, Doni, M, Verrecchia, A, Pelizzola, M, Amati, B, Sabò, A, Tesi, Alessandra, de Pretis, Stefano, Furlan, Mattia, Filipuzzi, Marco, Morelli, Marco J, Andronache, Adrian, Doni, Mirko, Verrecchia, Alessandro, Pelizzola, Mattia, Amati, Bruno, and Sabò, Arianna

Abstract

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.

Published
2019

2. Transcription of Mammalian cis-Regulatory Elements Is Restrained by Actively Enforced Early Termination

Author

Austenaa, Liv M I, Barozzi, Iros, Simonatto, Marta, Masella, Silvia, Della Chiara, Giulia, Ghisletti, Serena, Curina, Alessia, de Wit, Elzo, Bouwman, Britta A M, de Pretis, Stefano, Piccolo, Viviana, Termanini, Alberto, Prosperini, Elena, Pelizzola, Mattia, de Laat, Wouter, Natoli, Gioacchino, Austenaa, Liv M I, Barozzi, Iros, Simonatto, Marta, Masella, Silvia, Della Chiara, Giulia, Ghisletti, Serena, Curina, Alessia, de Wit, Elzo, Bouwman, Britta A M, de Pretis, Stefano, Piccolo, Viviana, Termanini, Alberto, Prosperini, Elena, Pelizzola, Mattia, de Laat, Wouter, and Natoli, Gioacchino

Published
2015

3. Transcription of Mammalian cis-Regulatory Elements Is Restrained by Actively Enforced Early Termination

Author

Austenaa, Liv M I, Barozzi, Iros, Simonatto, Marta, Masella, Silvia, Della Chiara, Giulia, Ghisletti, Serena, Curina, Alessia, de Wit, Elzo, Bouwman, Britta A M, de Pretis, Stefano, Piccolo, Viviana, Termanini, Alberto, Prosperini, Elena, Pelizzola, Mattia, de Laat, Wouter, Natoli, Gioacchino, Austenaa, Liv M I, Barozzi, Iros, Simonatto, Marta, Masella, Silvia, Della Chiara, Giulia, Ghisletti, Serena, Curina, Alessia, de Wit, Elzo, Bouwman, Britta A M, de Pretis, Stefano, Piccolo, Viviana, Termanini, Alberto, Prosperini, Elena, Pelizzola, Mattia, de Laat, Wouter, and Natoli, Gioacchino

Published
2015

4. Transcription of Mammalian cis-Regulatory Elements Is Restrained by Actively Enforced Early Termination

Author

Austenaa, Liv M I, Barozzi, Iros, Simonatto, Marta, Masella, Silvia, Della Chiara, Giulia, Ghisletti, Serena, Curina, Alessia, de Wit, Elzo, Bouwman, Britta A M, de Pretis, Stefano, Piccolo, Viviana, Termanini, Alberto, Prosperini, Elena, Pelizzola, Mattia, de Laat, Wouter, Natoli, Gioacchino, Austenaa, Liv M I, Barozzi, Iros, Simonatto, Marta, Masella, Silvia, Della Chiara, Giulia, Ghisletti, Serena, Curina, Alessia, de Wit, Elzo, Bouwman, Britta A M, de Pretis, Stefano, Piccolo, Viviana, Termanini, Alberto, Prosperini, Elena, Pelizzola, Mattia, de Laat, Wouter, and Natoli, Gioacchino

Abstract

Upon recruitment to active enhancers and promoters, RNA polymerase II (Pol II) generates short non-coding transcripts of unclear function. The mechanisms that control the length and the amount of ncRNAs generated by cis-regulatory elements are largely unknown. Here, we show that the adaptor protein WDR82 and its associated complexes actively limit such non-coding transcription. WDR82 targets the SET1 H3K4 methyltransferases and the nuclear protein phosphatase 1 (PP1) complexes to the initiating Pol II. WDR82 and PP1 also interact with components of the transcriptional termination and RNA processing machineries. Depletion of WDR82, SET1, or the PP1 subunit required for its nuclear import caused distinct but overlapping transcription termination defects at highly expressed genes and active enhancers and promoters, thus enabling the increased synthesis of unusually long ncRNAs. These data indicate that transcription initiated from cis-regulatory elements is tightly coordinated with termination mechanisms that impose the synthesis of short RNAs.

Published
2015

5. Transcription of Mammalian cis-Regulatory Elements Is Restrained by Actively Enforced Early Termination

Author

Austenaa, Liv M I, Barozzi, Iros, Simonatto, Marta, Masella, Silvia, Della Chiara, Giulia, Ghisletti, Serena, Curina, Alessia, de Wit, Elzo, Bouwman, Britta A M, de Pretis, Stefano, Piccolo, Viviana, Termanini, Alberto, Prosperini, Elena, Pelizzola, Mattia, de Laat, Wouter, Natoli, Gioacchino, Austenaa, Liv M I, Barozzi, Iros, Simonatto, Marta, Masella, Silvia, Della Chiara, Giulia, Ghisletti, Serena, Curina, Alessia, de Wit, Elzo, Bouwman, Britta A M, de Pretis, Stefano, Piccolo, Viviana, Termanini, Alberto, Prosperini, Elena, Pelizzola, Mattia, de Laat, Wouter, and Natoli, Gioacchino

Published
2015

6. Transcription of Mammalian cis-Regulatory Elements Is Restrained by Actively Enforced Early Termination

Author

Hubrecht Institute with UMC, Divisie Biomedische Genetica, Cancer, Austenaa, Liv M I, Barozzi, Iros, Simonatto, Marta, Masella, Silvia, Della Chiara, Giulia, Ghisletti, Serena, Curina, Alessia, de Wit, Elzo, Bouwman, Britta A M, de Pretis, Stefano, Piccolo, Viviana, Termanini, Alberto, Prosperini, Elena, Pelizzola, Mattia, de Laat, Wouter, Natoli, Gioacchino, Hubrecht Institute with UMC, Divisie Biomedische Genetica, Cancer, Austenaa, Liv M I, Barozzi, Iros, Simonatto, Marta, Masella, Silvia, Della Chiara, Giulia, Ghisletti, Serena, Curina, Alessia, de Wit, Elzo, Bouwman, Britta A M, de Pretis, Stefano, Piccolo, Viviana, Termanini, Alberto, Prosperini, Elena, Pelizzola, Mattia, de Laat, Wouter, and Natoli, Gioacchino

Published
2015

7. Transcription of Mammalian cis-Regulatory Elements Is Restrained by Actively Enforced Early Termination

Author

Austenaa, Liv M I, Barozzi, Iros, Simonatto, Marta, Masella, Silvia, Della Chiara, Giulia, Ghisletti, Serena, Curina, Alessia, de Wit, Elzo, Bouwman, Britta A M, de Pretis, Stefano, Piccolo, Viviana, Termanini, Alberto, Prosperini, Elena, Pelizzola, Mattia, de Laat, Wouter, Natoli, Gioacchino, Austenaa, Liv M I, Barozzi, Iros, Simonatto, Marta, Masella, Silvia, Della Chiara, Giulia, Ghisletti, Serena, Curina, Alessia, de Wit, Elzo, Bouwman, Britta A M, de Pretis, Stefano, Piccolo, Viviana, Termanini, Alberto, Prosperini, Elena, Pelizzola, Mattia, de Laat, Wouter, and Natoli, Gioacchino

Abstract

Upon recruitment to active enhancers and promoters, RNA polymerase II (Pol II) generates short non-coding transcripts of unclear function. The mechanisms that control the length and the amount of ncRNAs generated by cis-regulatory elements are largely unknown. Here, we show that the adaptor protein WDR82 and its associated complexes actively limit such non-coding transcription. WDR82 targets the SET1 H3K4 methyltransferases and the nuclear protein phosphatase 1 (PP1) complexes to the initiating Pol II. WDR82 and PP1 also interact with components of the transcriptional termination and RNA processing machineries. Depletion of WDR82, SET1, or the PP1 subunit required for its nuclear import caused distinct but overlapping transcription termination defects at highly expressed genes and active enhancers and promoters, thus enabling the increased synthesis of unusually long ncRNAs. These data indicate that transcription initiated from cis-regulatory elements is tightly coordinated with termination mechanisms that impose the synthesis of short RNAs.

Published
2015

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