Disease-Associated Short Tandem Repeats Co-localize with Chromatin Domain Boundaries.

ABSTRACT: More than 25 inherited human disorders are caused by the unstable expansion of repetitive DNA sequences termed short tandem repeats (STRs). A fundamental unresolved question is why some STRs are susceptible to pathologic expansion, whereas thousands of repeat tracts across the human genome are relatively stable. Here, we discover that nearly all disease-associated STRs (daSTRs) are located at boundaries demarcating 3D chromatin domains. We identify a subset of boundaries with markedly higher CpG island density compared to the rest of the genome. daSTRs specifically localize to ultra-high-density CpG island boundaries, suggesting they might be hotspots for epigenetic misregulation or topological disruption linked to STR expansion. Fragile X syndrome patients exhibit severe boundary disrupti

SUBMITTER: Sun JH 

PROVIDER: S-EPMC6175607 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature