EpigenomicsNov 24, 2025

CTCF's role in shaping DNA structure and controlling RNA modifications

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗

Updated Jan 7, 2026

Abstract

CCCTC-binding factor (CTCF) plays a crucial role in both DNA and RNA biology, influencing gene expression and cellular responses.

CTCF is a highly conserved protein that regulates transcriptional processes by organizing chromatin and defining gene interactions.
It establishes topologically associated domains that can either promote or inhibit the transcription of genes.
CTCF interacts with nascent RNA, pre-mRNA, and long non-coding RNAs, affecting various aspects of RNA dynamics.
Recent findings in epitranscriptomics reveal that RNA modifications, such as N6-methyladenosine and pseudouridine, regulate RNA stability and processing.
Disruption of CTCF function or RNA modifications is associated with cancer development, developmental disorders, and treatment resistance.

Simplified

Transcriptional regulation is a crucial biological process that enables accurate gene expression, allowing cells to maintain their identity and respond to environmental stimuli. CCCTC-binding factor is a fundamental protein that actively involves itself in transcriptional regulation, serving as a highly conserved architectural regulator. CTCF is traditionally acknowledged for its function in chromatin organization and insulation. It coordinates active or repressed transcription by establishing topologically associated domains and also helps in preserving enhancer-promoter identity. In addition to its DNA-binding roles, CTCF significantly participates in RNA biology. It engages with nascent RNA, pre-mRNA, and long non-coding RNAs via its RNA-binding domain, thereby affecting different transcriptional dynamics. Simultaneously, the swiftly advancing domain of epitranscriptomics has revealed other RNA modifications, such as N6-methyladenosine (mA), 5-methylcytosine (mC), and pseudouridine (Ψ), which jointly regulate RNA stability, transport, translation, and destruction. Hence, the dysregulation of these changes or CTCFactivity is closely linked to oncogenesis, developmental problems, and resistance to therapy. The intersection of CTCF-mediated genomic architecture with epitranscriptomic regulation highlights its function as a complex integrator of chromatin and RNA networks. This review consolidates contemporary understanding of CTCF's twin activities in DNA and RNA binding, examining how their interaction influences transcriptional regulation, RNA processing, and disease relevance. 6 5

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The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript.

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CTCF's role in shaping DNA structure and controlling RNA modifications

Abstract

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