Identification of a Molecular Signature for Barrier Insulators
Factor co-localization at the erythroid ankyrin promoter as determined by Chromatin Immunoprecipitation coupled with high throughput sequencing (ChIP-seq). The region upstream of the ankyrin promoter has been shown to function as a barrier, and mutations which disrupt the barrier function of this region are associated with hereditary spherocytosis,1 an inherited hemolytic anemia.
Barrier insulators function to actively maintain the boundaries between heterochromatin (inactive DNA) and euchromatin (actively transcribed DNA). They are critical for regulation of cell-type specific gene expression in normal development and differentiation. Mutations that disrupt barrier insulator function have been associated with developmental disorders, malignancies, and inherited hemolytic anemias. Barrier insulators are poorly understood in mammalian cells, with much of the available data coming from model organisms.
This project combines genome-wide studies of barrier-associated factors with functional assays to identify a common regulatory signal for cell-type specific, functional, barrier insulators in primary human erythroid cells.
Unbiased identification of barrier insulators on a genome wide scale will provide novel insights into normal erythropoiesis and its perturbation in human disease.
1. Gallagher et al. J Clin Invest. 2010 Dec;120(12):4453-65.