Faculty Opinions recommendation of A protein activity assay to measure global transcription factor activity reveals determinants of chromatin accessibility.

Author(s):  
Lars Malmstroem
2018 ◽  
Vol 36 (6) ◽  
pp. 521-529 ◽  
Author(s):  
Bei Wei ◽  
Arttu Jolma ◽  
Biswajyoti Sahu ◽  
Lukas M Orre ◽  
Fan Zhong ◽  
...  

2018 ◽  
Author(s):  
Ignacio J. Tripodi ◽  
Mary A. Allen ◽  
Robin D. Dowell

AbstractTranscription factors are managers of the cellular factory, and key components to many diseases. Many non-coding single nucleotide polymorphisms affect transcription factors, either by directly altering the protein or its functional activity at individual binding sites. Here we first briefly summarize high throughput approaches to studying transcription factor activity. We then demonstrate, using published chromatin accessibility data (specifically ATAC-seq), that the genome wide profile of TF recognition motifs relative to regions of open chromatin can determine the key transcription factor altered by a perturbation. Our method of determining which TF are altered by a perturbation is simple, quick to implement and can be used when biological samples are limited. In the future, we envision this method could be applied to determining which TFs show altered activity in response to a wide variety of drugs and diseases.


Author(s):  
Stephen P. Methot ◽  
Jan Padeken ◽  
Giovanna Brancati ◽  
Peter Zeller ◽  
Colin E. Delaney ◽  
...  

AbstractThe developmental role of histone H3K9 methylation (H3K9me), which typifies heterochromatin, remains unclear. In Caenorhabditis elegans, loss of H3K9me leads to a highly divergent upregulation of genes with tissue and developmental-stage specificity. During development H3K9me is lost from differentiated cell type-specific genes and gained at genes expressed in earlier developmental stages or other tissues. The continuous deposition of H3K9me2 by the SETDB1 homolog MET-2 after terminal differentiation is necessary to maintain repression. In differentiated tissues, H3K9me ensures silencing by restricting the activity of a defined set of transcription factors at promoters and enhancers. Increased chromatin accessibility following the loss of H3K9me is neither sufficient nor necessary to drive transcription. Increased ATAC-seq signal and gene expression correlate at a subset of loci positioned away from the nuclear envelope, while derepressed genes at the nuclear periphery remain poorly accessible despite being transcribed. In conclusion, H3K9me deposition can confer tissue-specific gene expression and maintain the integrity of terminally differentiated muscle by restricting transcription factor activity.


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