Allele-Specific Regulation of TCRβ Variable Gene Segment Chromatin Structure

Regulation of TCR δ and α repertoires by local and long-distance control of variable gene segment chromatin structure

Murine Tcrd and Tcra gene segments reside in a single genetic locus and undergo recombination in CD4- CD8- (double negative [DN]) and CD4+ CD8+ (double positive [DP]) thymocytes, respectively. TcraTcrd locus variable gene segments are subject to complex regulation. Only a small subset of approximately 100 variable gene segments contributes substantially to the adult TCRdelta repertoire. Moreove...

Roles of Chromatin insulators in gene regulation and diseases

With advances in genetic science, the dynamic structure of eukaryotic genome is considered as basis of gene expression regulation. Long-distance communication between regulatory elements and target promoters is critical and the mechanisms responsible for this connection are just starting to emerge. Chromatin insulators are key determinants of proper gene regulation and precise organization of c...

Regulation of TCRβ allelic exclusion by gene segment proximity and accessibility.

Ag receptor loci are regulated to promote allelic exclusion, but the mechanisms are not well understood. Assembly of a functional TCR β-chain gene triggers feedback inhibition of V(β)-to-DJ(β) recombination in double-positive (DP) thymocytes, which correlates with reduced V(β) chromatin accessibility and a locus conformational change that separates V(β) from DJ(β) gene segments. We previously g...

Allele-Specific Regulation of TCR

Allele-Specific Gene Silencing

Cardiac arrhythmias are a major healthcare problem in the developed world. The American Heart Association 2017 statistical report indicates that atrial fibrillation, the most common cardiac rhythm disorder, has an ≈25% lifetime incidence and annual costs of ≈26 billion dollars, whereas sudden cardiac death (usually caused by malignant arrhythmias) affects fewer individuals (just under 200 000 A...