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Structural Basis for the Recognition of Non-methylated DNA by the CXXC Domain
1Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan 430079, PR China.
Abstract:
CXXC domain-containing proteins are often involved in different biological processes, such as cell proliferation and development, apoptosis, DNA repair, signaling transduction, and tumorigenesis, by regulating transcription. 12 CXXC domain-containing proteins have been identified in human, and structural together with DNA binding studies reveal that these CXXC domains, a 50-70 residues module of two conserved CXXCXXC motifs, bind to non-methylated DNA in different sequence contexts. These CXXC domain-containing proteins and their complexes regulate various biological processes, and the CXXC domain plays an important role in the recruitment and regulation of their associated chromatin-modifying activities. In this review, we summarize these human CXXC domain-containing proteins in terms of their structures, biology, and biochemistry, and also discuss how they mediate cross-talk among different epigenetic modifications.
Insights
Human CXXC domain-containing proteins regulate transcription and epigenetic modifications. This review details their structures, biology, and biochemical roles in processes like DNA repair and tumorigenesis.
Area of Science:
- Molecular Biology
- Epigenetics
- Protein Structure
Background:
- CXXC domain-containing proteins regulate critical cellular functions including transcription, cell proliferation, apoptosis, DNA repair, and tumorigenesis.
- Twelve such proteins exist in humans, featuring a conserved CXXC domain (50-70 residues) with two CXXCXXC motifs.
- This domain facilitates binding to non-methylated DNA across various sequence contexts.
Purpose of the Study:
- To review human CXXC domain-containing proteins.
- To summarize their structures, biological functions, and biochemical properties.
- To discuss their role in mediating cross-talk between epigenetic modifications.
Main Methods:
- Structural analysis of CXXC domains.
- DNA-binding studies.
- Biochemical characterization of CXXC domain-containing proteins and their complexes.
- Review of existing literature on human CXXC domain-containing proteins.
Main Results:
- The CXXC domain is crucial for DNA binding and protein complex formation.
- These proteins are key regulators of transcription and chromatin modification.
- CXXC domain proteins mediate interactions among diverse epigenetic modifications.
Conclusions:
- Human CXXC domain-containing proteins are vital regulators of gene expression and epigenetic processes.
- Understanding their structure-function relationship is key to deciphering their roles in health and disease.
- These proteins offer potential targets for therapeutic interventions in epigenetic-related disorders.
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