An RNA polymerase III tissue and tumor atlas uncovers context-specific activities linked to 3D epigenome regulatory mechanisms
Contact us if these videos are not relevant.
Contact us if these videos are not relevant.
View abstract on PubMed
Summary
This summary is machine-generated.This study maps human RNA polymerase III (Pol III) activity across tissues and cancers using chromatin accessibility. Pol III activity varies by tissue, contracting in heart/brain and expanding in cancers, linking it to nuclear organization.
Area Of Science
- Molecular Biology
- Genomics
- Epigenetics
Background
- RNA polymerase III (Pol III) transcribes small noncoding RNAs crucial for cellular functions.
- Understanding Pol III gene-level dynamics and tissue-specific expression is limited by technical challenges.
Purpose Of The Study
- To create a predictive map of human Pol III activity across multiple tissues and cancer subtypes.
- To define the core Pol III transcriptome and identify context-specific genes.
Main Methods
- Profiling chromatin accessibility (ATAC-seq) at Pol III-transcribed genes.
- Utilizing uniform binary classification to infer Pol III transcription from accessibility data.
- Analyzing gene uniformity across different cellular contexts.
Main Results
- Developed a multi-tissue map of human Pol III activity across 19 tissues and 23 cancer subtypes.
- Identified a core Pol III transcriptome and cataloged context-specific genes.
- Observed Pol III transcriptome contraction in heart and brain, and expansion in cancers.
- Found tissue- and tumor-specific Pol III genes enriched in lamina-associated domains (LADs).
- Demonstrated that altered nuclear lamin expression can induce Pol III patterns in tumors.
Conclusions
- Pol III activity exhibits significant tissue- and tumor-specific variation.
- Pol III dynamics are linked to subnuclear compartmentalization (LADs).
- Provides a resource for understanding Pol III function and small RNA biogenesis in health and disease, particularly cancer.
Contact us if these videos are not relevant.
Contact us if these videos are not relevant.
Related Concept Videos
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
In most mammals, females have two X chromosomes (XX) while males have an X and a Y chromosome (XY). The X chromosome contains significantly more genes than the Y chromosome. Therefore, to prevent an excess of X chromosome-linked gene expression in females, one of the two X chromosomes is randomly silenced during early development....
RNA Polymerase (RNAP) is conserved in all animals, with bacterial, archaeal, and eukaryotic RNAPs sharing significant sequence, structural, and functional similarities. Among the three eukaryotic RNAPs, RNA Polymerase II is most similar to bacterial RNAP in terms of both structural organization and folding topologies of the enzyme subunits. However, these similarities are not reflected in their mechanism of action.
All three eukaryotic RNAPs require specific transcription factors, of which the...
Chromatin is the massive complex of DNA and proteins packaged inside the nucleus. The complexity of chromatin folding and how it is packaged inside the nucleus greatly influences access to genetic information. Generally, the nucleus' periphery is considered transcriptionally repressive, while the cell's interior is considered a transcriptionally active area.
Topologically Associated Domains (TADs)
The 3-dimensional positioning of chromatin in the nucleus influences the...