Interaction of the glucocorticoid receptor with the chromatin landscape.
The generality and spectrum of chromatin-remodeling requirements for nuclear receptor function are unknown. We have characterized glucocorticoid receptor (GR) binding events and chromatin structural transitions across GR-induced or -repressed genes. This analysis reveals that GR binding invariably occurs at nuclease-accessible sites (DHS). A remarkable diversity of mechanisms, however, render these sites available for GR binding. Accessibility of the GR binding sites is either constitutive or hormone inducible. Within each category, some DHS sites require the Brg1-containing Swi/Snf complex, but others are Brg1 independent, implicating a different remodeling complex. The H2A.Z histone variant is highly enriched at both inducible and constitutive DHS sites and is subject to exchange during hormone activation. The DHS profile is highly cell specific, implicating cell-selective organization of the chromatin landscape as a critical determinant of tissue-selective receptor function. Furthermore, the widespread requirement for chromatin remodeling supports the recent hypothesis that the rapid exchange of receptor proteins occurs during nucleosome reorganization.
John
Sam
S
Laboratory of Receptor Biology and Gene Expression, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892-5055, USA.
Sabo
Peter J
PJ
Johnson
Thomas A
TA
Sung
Myong-Hee
MH
Biddie
Simon C
SC
Lightman
Stafford L
SL
Voss
Ty C
TC
Davis
Sean R
SR
Meltzer
Paul S
PS
Stamatoyannopoulos
John A
JA
Hager
Gordon L
GL
D000818:Animals; D002460:Cell Line; D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006657:Histones / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D009698:Nucleoproteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011485:Protein Binding; D012313:RNA / Q000235:genetics / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D006657:Histones; D009687:Nuclear Proteins; D009698:Nucleoproteins; D011965:Receptors, Glucocorticoid; C445179:SWI-SNF-B chromatin-remodeling complex; D014157:Transcription Factors; D012313:RNA; C084108:SMARCA4 protein, human; D004265:DNA Helicases