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MYC-Associated Factor MAX is an Essential Regulator of the Clock Core Network

49 Pages Posted: 19 Aug 2019 Publication Status: Review Complete

See all articles by Olga Blazevits

Olga Blazevits

Fondazione Istituto Italiano di Tecnologia (IIT) - Molecular Medicine Research Line

Nityanand Bolshette

Fondazione Istituto Italiano di Tecnologia (IIT) - Molecular Medicine Research Line

Donatella Vecchio

Fondazione Istituto Italiano di Tecnologia (IIT) - Molecular Medicine Research Line

Ana Guijarro

Fondazione Istituto Italiano di Tecnologia (IIT) - Molecular Medicine Research Line

Ottavio Croci

Fondazione Istituto Italiano di Tecnologia (IIT) - Center for Genomic Science

Stefano Campaner

Fondazione Istituto Italiano di Tecnologia (IIT) - Center for Genomic Science

Benedetto Grimaldi

Fondazione Istituto Italiano di Tecnologia (IIT) - Molecular Medicine Research Line

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Abstract

The circadian transcriptional network is based on a competition between transcriptional activator and repressor complexes regulating the rhythmic expression of clock-controlled genes. We show here that the MYC-Associated factor X, MAX, plays a repressive role in this network and operates through its MYC-independent binding to E-box-containing regulatory regions within the promoters of circadian BMAL1 targets. This clock function of MAX is essential for maintaining a proper circadian rhythm but separated by the role of MAX as a partner of MYC in controlling cell proliferation. We also identified MAX Network Transcriptional repressor, MNT, as a fundamental partner of MAX-mediated circadian regulation. Collectively, our data indicate that MAX is an integral part of the core molecular clock and keeps the balance between positive and negative elements of the molecular clock machinery. Accordingly, alteration of MAX transcriptional complexes may contribute to circadian dysfunction in pathological contexts.

Keywords: MYC-associated factor X, clock transcriptional network, MAX network, MNT, BMAL1, MYC-independent, E-box-mediated transcription, stoichiometric balance

Suggested Citation

Blazevits, Olga and Bolshette, Nityanand and Vecchio, Donatella and Guijarro, Ana and Croci, Ottavio and Campaner, Stefano and Grimaldi, Benedetto, MYC-Associated Factor MAX is an Essential Regulator of the Clock Core Network (August 16, 2019). Available at SSRN: https://ssrn.com/abstract=3438375 or http://dx.doi.org/10.2139/ssrn.3438375
This version of the paper has not been formally peer reviewed.

Olga Blazevits

Fondazione Istituto Italiano di Tecnologia (IIT) - Molecular Medicine Research Line

Italy

Nityanand Bolshette

Fondazione Istituto Italiano di Tecnologia (IIT) - Molecular Medicine Research Line

Italy

Donatella Vecchio

Fondazione Istituto Italiano di Tecnologia (IIT) - Molecular Medicine Research Line

Italy

Ana Guijarro

Fondazione Istituto Italiano di Tecnologia (IIT) - Molecular Medicine Research Line

Italy

Ottavio Croci

Fondazione Istituto Italiano di Tecnologia (IIT) - Center for Genomic Science

Italy

Stefano Campaner

Fondazione Istituto Italiano di Tecnologia (IIT) - Center for Genomic Science

Italy

Benedetto Grimaldi (Contact Author)

Fondazione Istituto Italiano di Tecnologia (IIT) - Molecular Medicine Research Line ( email )

Italy

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