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

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

doi:10.1016/j.molcel.2015.09.018

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

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

Hubrecht Institute

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

71 Citations (Scopus)

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.

Original language	English
Pages (from-to)	460-74
Number of pages	15
Journal	Molecular Cell
Volume	60
Issue number	3
DOIs	https://doi.org/10.1016/j.molcel.2015.09.018
Publication status	Published - 05 Nov 2015

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Austenaa, L. M. I., Barozzi, I., Simonatto, M., Masella, S., Della Chiara, G., Ghisletti, S., Curina, A., de Wit, E., Bouwman, B. A. M., de Pretis, S., Piccolo, V., Termanini, A., Prosperini, E., Pelizzola, M., de Laat, W., & Natoli, G. (2015). Transcription of Mammalian cis-Regulatory Elements Is Restrained by Actively Enforced Early Termination. Molecular Cell, 60(3), 460-74. https://doi.org/10.1016/j.molcel.2015.09.018

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title = "Transcription of Mammalian cis-Regulatory Elements Is Restrained by Actively Enforced Early Termination",

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.",

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

year = "2015",

month = nov,

day = "5",

doi = "10.1016/j.molcel.2015.09.018",

language = "English",

volume = "60",

pages = "460--74",

journal = "Molecular Cell",

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publisher = "Cell Press",

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Austenaa, LMI, Barozzi, I, Simonatto, M, Masella, S, Della Chiara, G, Ghisletti, S, Curina, A, de Wit, E, Bouwman, BAM, de Pretis, S, Piccolo, V, Termanini, A, Prosperini, E, Pelizzola, M, de Laat, W & Natoli, G 2015, 'Transcription of Mammalian cis-Regulatory Elements Is Restrained by Actively Enforced Early Termination', Molecular Cell, vol. 60, no. 3, pp. 460-74. https://doi.org/10.1016/j.molcel.2015.09.018

TY - JOUR

T1 - Transcription of Mammalian cis-Regulatory Elements Is Restrained by Actively Enforced Early Termination

AU - Austenaa, Liv M I

AU - Barozzi, Iros

AU - Simonatto, Marta

AU - Masella, Silvia

AU - Della Chiara, Giulia

AU - Ghisletti, Serena

AU - Curina, Alessia

AU - de Wit, Elzo

AU - Bouwman, Britta A M

AU - de Pretis, Stefano

AU - Piccolo, Viviana

AU - Termanini, Alberto

AU - Prosperini, Elena

AU - Pelizzola, Mattia

AU - de Laat, Wouter

AU - Natoli, Gioacchino

PY - 2015/11/5

Y1 - 2015/11/5

N2 - 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.

AB - 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.

U2 - 10.1016/j.molcel.2015.09.018

DO - 10.1016/j.molcel.2015.09.018

M3 - Article

C2 - 26593720

SN - 1097-2765

VL - 60

SP - 460

EP - 474

JO - Molecular Cell

JF - Molecular Cell

IS - 3

ER -

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

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