Pathologically Relevant Prelamin A Interactions with Transcription Factors
Arantza Infante1, Clara I Rodríguez1
1Stem Cells and Cell Therapy Laboratory, BioCruces Health Research Institute, Cruces University Hospital, Barakaldo, Spain.
Methods in Enzymology
|January 19, 2016
Summary
LMNA-linked diseases cause toxic prelamin A buildup, disrupting nuclear structure. This study models laminopathy in human mesenchymal stem cells to investigate its effects on transcription factors.
Area of Science:
- Cell Biology
- Genetics
- Biochemistry
Background:
- LMNA-linked laminopathies result from mutations or processing defects of prelamin A.
- Accumulation of farnesylated prelamin A (progerin or immature prelamin A) disrupts nuclear lamina structure and cellular function.
- Aberrant lamin networks may trap transcription factors, impairing their activity, particularly in mesenchymal tissues.
Purpose of the Study:
- To establish an experimental model of laminopathy in human mesenchymal stem cells (hMSCs).
- To investigate the hypothesis that accumulated prelamin A interferes with transcription factor activity.
- To provide protocols for inducing and detecting prelamin A accumulation in hMSCs.
Main Methods:
- Induction of prelamin A accumulation in hMSCs.
- Development of protocols for detecting prelamin A accumulation.
- Bioinformatic analysis of transcription factors.
- In vitro assays to assess transcription factor activity.
Main Results:
- Successful generation of an experimental model of prelamin A accumulation in hMSCs.
- Detailed protocols for induction and detection are provided.
- Bioinformatic and in vitro analyses identified potentially affected transcription factors.
Conclusions:
- The developed hMSC model is suitable for studying LMNA-linked laminopathies.
- Prelamin A accumulation may disrupt transcription factor function in mesenchymal cells.
- Further research can elucidate the precise mechanisms of transcription factor interference.
Related Concept Videos
02:36RNA Polymerase II Accessory Proteins
11.3K
Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
11.3K
02:41Chromatin Structure Regulates pre-mRNA Processing
8.4K
In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
The chromatin structure, especially...
The chromatin structure, especially...
8.4K
02:16Transcription Factors
83.9K
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
83.9K
02:16Transcription Factors
26.8K
26.8K
02:04Co-activators and Co-repressors
8.8K
Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
8.8K
02:04Co-activators and Co-repressors
3.2K
3.2K