Recruitment of CTCF to the SIRT1 promoter after Oxidative Stress mediates Cardioprotective Transcription
Year: 2024
Type: preprint
Abstract: ABSTRACT Because most DNA-binding transcription factors (dbTFs), including the architectural regulator CTCF, bind RNA and exhibit di-/multimerization, a central conundrum is whether these distinct properties are regulated post-transcriptionally to modulate transcriptional programs. Here, investigating stress-dependent activation of SIRT1, encoding an evolutionarily-conserved protein deacetylase, we show that induced phosphorylation of CTCF acts as a rheostat to permit CTCF occupancy of low-affinity promoter DNA sites to precisely the levels necessary. This CTCF recruitment to the SIRT1 promoter is eliciting a cardioprotective cardiomyocyte transcriptional activation program and provides resilience against the stress of the beating heart in vivo . Mice harboring a mutation in the conserved low-affinity CTCF promoter binding site exhibit an altered, cardiomyocyte-specific transcriptional program and a systolic heart failure phenotype. This transcriptional role for CTCF reveals that a covalent dbTF modification regulating signal-dependent transcription serves as a previously unsuspected component of the oxidative stress response.
Authors: Tobias Wagner, Priyanka Priyanka, Rudi Micheletti, Meyer J. Friedman, Sreejith J. Nair, Amir Gamliel, Havilah Taylor, Xiaoyuan Song, Miook Cho, Soohwan Oh, Wenbo Li, Jeehae Han, Kenneth A. Ohgi, Madeline Abrass, Agnieszka D’Antonio-Chronowska, Matteo D’Antonio, Helen Hazuda, Ravindranath Duggirala, John Blangero, Sheng Ding, Carlos Guzmann, Kelly A. Frazer, Aneel K. Aggarwal, Alice E. Zemljic-Harpf, Michael G. Rosenfeld, Yousin Suh
Institutions: University of California San Diego, Georgetown University, University of Science and Technology of China, Albert Einstein College of Medicine, Korea University, The University of Texas Health Science Center at Houston, Columbia University, The University of Texas Rio Grande Valley, Texas A&M University – San Antonio, Gladstone Institutes, Icahn School of Medicine at Mount Sinai, VA San Diego Healthcare System
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W4398137822