Insight into GATA1 transcriptional activity through interrogation of cis elements disrupted in human erythroid disorders.

ABSTRACT: Whole-exome sequencing has been incredibly successful in identifying causal genetic variants and has revealed a number of novel genes associated with blood and other diseases. One limitation of this approach is that it overlooks mutations in noncoding regulatory elements. Furthermore, the mechanisms by which mutations in transcriptionalcis-regulatory elements result in disease remain poorly understood. Here we used CRISPR/Cas9 genome editing to interrogate three such elements harboring mutations in human erythroid disorders, which in all cases are predicted to disrupt a canonical binding motif for the hematopoietic transcription factor GATA1. Deletions of as few as two to four nucleotides resulted in a substantial decrease (>80%) in target gene expression. Isolated deletions of the canonic

SUBMITTER: Wakabayashi A 

PROVIDER: S-EPMC4843446 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature