Poster Sessions

GENO -24

Simon Biddie

S. Biddie, S. John, M. Sung, T. Johnson, P. Sabo, J. Stamatoyannopoulos, G. Hager

Massively parallel sequencing reveals cell-specific interactions of the glucocorticoid receptor with chromatin transitions

Transcription factor interactions with DNA occur in the context of a highly organized chromatin landscape. A requirement for transcription factors to bind their target sequences in DNA requires an accessible chromatin environment. The glucocorticoid receptor (GR) is part of the nuclear receptor family of transcription factors, activating or repressing genes in a hormone-dependent fashion. Using massively parallel signature sequencing (MPSS), we have characterized genome-wide occupancy of GR binding events (ChIP-Seq) and measured changes in local chromatin transitions using DNaseI as a probe for chromatin accessibility (DNase-Seq). Genome-wide analysis in multiple cell lines, a mammary adenocarcincoma cell line (3134) and a pituitary corticotroph cell line (AtT-20), demonstrate that GR invariably binds to regions of accessible chromatin. We observe that GR binding can occur at constitutive or GR-mediated local chromatin remodeling events. We also observe that these events are concordant with cell-specific DNaseI hypersensitive sites. The cell-specific conjunction of binding events with chromatin transitions reveals an important mechanism for cell-specific expression of GR responsive genes. Computational and bioinformatic analysis of GR binding events in multiple cell lines will be discussed. We propose that GR binding at sites local chromatin transitions are common mechanisms for all GR interactions with chromatin in vivo.