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Updated: Jun 21, 2025

Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
Published on: September 20, 2018
ZC3H4/Restrictor Exerts a Stranglehold on Pervasive Transcription
1The Living Systems Institute, University of Exeter, Stocker Road, Exeter EX4 4QD, UK.
Abstract:
The regulation of transcription by RNA polymerase II (RNAPII) underpins all cellular processes and is perturbed in thousands of diseases. In humans, RNAPII transcribes ∼20000 protein-coding genes and engages in apparently futile non-coding transcription at thousands of other sites. Despite being so ubiquitous, this transcription is usually attenuated soon after initiation and the resulting products are immediately degraded by the nuclear exosome. We and others have recently described a new complex, "Restrictor", which appears to control such unproductive transcription. Underpinned by the RNA binding protein, ZC3H4, Restrictor curtails unproductive/pervasive transcription genome-wide. Here, we discuss these recent discoveries and speculate on some of the many unknowns regarding Restrictor function and mechanism.
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