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Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
Published on: September 20, 2018
Coordination of epigenetic events
1Baker Medical Research Institute, Epigenetics in Human Health and Disease Laboratory, The Alfred Medical Research and Education Precinct (AMREP), Prahran, Victoria, Australia. assam.el-osta@baker.edu.au
Abstract:
During the course of DNA damage a complex repertoire of molecular signals, chromatin determinants and specific transcription factors are set in motion for repair. In many instances, the response pathway can be characterized by profound changes in molecular remodeling and is intimately linked with DNA replication and gene transcription. Our understanding of the molecular pathways has come from scientific developments that represent many disparate disciplines, such as cancer (epi)genetics, chromatin modifications during cellular development and the emerging prominence of epigenetic events in human disease. These multidisciplinary areas reveal a functional relationship and suggest that repair and transcription must coincide in the context of chromatin. We have come to appreciate the repair process and the role of transcriptional components in a sophisticated program of epigenetic regulation, and we have learnt much since the first description of the nucleosome as a spheroid disklike unit. The coordinated and ordered response to DNA damage can specify structures that mobilize and remodel nucleosomes. Investigators will undoubtedly continue to explore the structural and functional states of DNA damage repair and continue to profile the sequence of events and scrutinize the molecular signatures that specify these changes in chromatin dynamics, genomic stability and transcriptional performance. In this special issue, authors have contributed reviews that discuss hypotheses and results regarding DNA damage repair and transcription. The topics covered range from DNA repair in a chromatin environment to the deadly double-strand break, histone modifications to ATP-dependent chromatin remodeling, gene silencing in cancer to apoptosis and regulation of chromatin dynamics by DNA methylation. The scene is set for a new view of damage detection and repair by the coordination of epigenetic states.
Insights
DNA damage repair involves complex molecular signals and chromatin changes, closely linked with gene transcription and epigenetic regulation. Understanding these coordinated processes is crucial for genomic stability and disease insights.
Area of Science:
- Molecular Biology
- Epigenetics
- Genomics
Background:
- DNA damage triggers a complex response involving molecular signals, chromatin determinants, and transcription factors for repair.
- This response is intricately linked with DNA replication and gene transcription, highlighting the interplay between repair and cellular processes.
- Advances in cancer (epi)genetics, chromatin modifications, and epigenetic events in disease have illuminated these molecular pathways.
Purpose of the Study:
- To review current understanding of DNA damage repair mechanisms within the chromatin environment.
- To explore the functional relationship between DNA repair, gene transcription, and epigenetic regulation.
- To present hypotheses and results on DNA damage repair and transcription from diverse scientific contributions.
Main Methods:
- Review of multidisciplinary scientific literature.
- Synthesis of findings from cancer (epi)genetics, chromatin modifications, and epigenetic events.
- Compilation of contributions discussing DNA repair in chromatin, histone modifications, and DNA methylation.
Main Results:
- DNA damage repair is a sophisticated program of epigenetic regulation involving nucleosome remodeling.
- A coordinated response to DNA damage involves specific structures that mobilize and remodel nucleosomes.
- Functional relationships reveal that repair and transcription must coincide within the chromatin context.
Conclusions:
- The coordinated response to DNA damage involves epigenetic states, influencing chromatin dynamics, genomic stability, and transcriptional performance.
- Continued investigation into structural and functional states of DNA damage repair is essential.
- A new perspective on damage detection and repair emerges from the coordination of epigenetic states.
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