Non-coding RNAs (ncRNAs) transcribed from the promoter and the downstream region can affect the expression of the corresponding coding genes. It has been shown that sense-directed ncRNAs arising from the promoter region of the E-cadherin gene (CDH1) mediate its repression. Here, we show that an antisense-directed ncRNA (paRCDH1-AS) transcribed from the CDH1 promoter is necessary for its expression. paRCDH1-AS acts as a hooking scaffold by recruiting the epigenetic regulators, UHRF1, DNMT3A, SUV39H1 and SUZ12, involved in CDH1 repression. The binding of epigenetic regulators to paCRDH1-AS, indeed, prevents their localization to the chromatin on CDH1 promoter. Moreover, paRCDH1-AS silencing induces CDH1 repression and a switch of the epigenetic profile on the promoter towards a more closed chromatin. Using bioinformatic and experimental approaches we defined that the promoter of the paRCDH1-AS is shared with the E-cadherin gene, showing a bidirectional promoter activity. We found that UHRF1 controls both CDH1 and paRCDH1-AS by directly binding this bidirectional promoter region. Our study provides evidences, for the first time, that UHRF1 recruitment can be affected by promoter-associated non-coding RNAs, opening new perspective regarding the role of UHRF1 in these complex regulatory networks.

UHRF1 regulates CDH1 via promoter associated non-coding RNAs in prostate cancer cells

Magnani, Elena
Membro del Collaboration Group
;
Macchi, Filippo
Membro del Collaboration Group
;
Mancini, Monica
Membro del Collaboration Group
;
LOMAZZI, VANESSA VERONICA
Membro del Collaboration Group
;
COGLIATI, SARA
Validation
;
Pistore, Christian
Investigation
;
Mandruzzato, Martina
Investigation
;
Bonapace, Ian Marc
Conceptualization
2018-01-01

Abstract

Non-coding RNAs (ncRNAs) transcribed from the promoter and the downstream region can affect the expression of the corresponding coding genes. It has been shown that sense-directed ncRNAs arising from the promoter region of the E-cadherin gene (CDH1) mediate its repression. Here, we show that an antisense-directed ncRNA (paRCDH1-AS) transcribed from the CDH1 promoter is necessary for its expression. paRCDH1-AS acts as a hooking scaffold by recruiting the epigenetic regulators, UHRF1, DNMT3A, SUV39H1 and SUZ12, involved in CDH1 repression. The binding of epigenetic regulators to paCRDH1-AS, indeed, prevents their localization to the chromatin on CDH1 promoter. Moreover, paRCDH1-AS silencing induces CDH1 repression and a switch of the epigenetic profile on the promoter towards a more closed chromatin. Using bioinformatic and experimental approaches we defined that the promoter of the paRCDH1-AS is shared with the E-cadherin gene, showing a bidirectional promoter activity. We found that UHRF1 controls both CDH1 and paRCDH1-AS by directly binding this bidirectional promoter region. Our study provides evidences, for the first time, that UHRF1 recruitment can be affected by promoter-associated non-coding RNAs, opening new perspective regarding the role of UHRF1 in these complex regulatory networks.
http://www.elsevier.com/wps/find/journaldescription.cws_home/713381/description#description
Bidirectional promoters; CDH1; Promoter-associated non-coding RNAs; UHRF1;
Magnani, Elena; Macchi, Filippo; Mancini, Monica; Lomazzi, VANESSA VERONICA; Cogliati, Sara; Pistore, Christian; Mandruzzato, Martina; Dock-Bregeon, Anne-Catherine; Bonapace, Ian Marc
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11383/2069036
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