title: Chromatin structure analysis of the human c-fos promoter reveals a centrally positioned nucleosome.
abstract: Chromatin architecture plays an important regulatory role in nuclear transcription in eukaryotes. In particular, a preset chromatin organization has been proposed to prime rapidly inducible genes for response to extracellular signals. We analyzed the chromatin architecture of the rapidly inducible human c-fos gene using a combination of nuclease digestion studies. Several regions of nuclease sensitivity in the c-fos gene are observed: (i) a hypersensitive site at position -1900; (ii) a region centered at -350 that corresponds to the locations of the serum response element (SRE) and the sis-inducible element (SIE); (iii) a region around the transcriptional start site that includes the TATA box, the cAMP-responsive element (CRE) and a directly repeated sequence (DRE); and (iv) two sites at positions +250 and +550 that appear to delineate the linker regions of two positioned nucleosomes. In contrast, the region from -280 to -90 is strongly resistant to nuclease digestion. We identify a highly positioned nucleosome in this region of the c-fos promoter that may contribute to a defined higher-order nucleoprotein structure containing the nucleosome and proteins bound to the SIE, SRE, DRE, and CRE elements and TATA box. This structure may lead to a functional juxtaposition of the regulatory elements of the c-fos promoter and suggests that such a chromatin architecture is particularly suited for presetting promoters for rapid responsiveness.
authors.affiliation: Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA.
authors.forename: R E
authors.initials: RE
authors.lastname: Herrera
authors.forename: A
authors.initials: A
authors.lastname: Nordheim
authors.forename: A F
authors.initials: AF
authors.lastname: Stewart
mesh_terms: D001665:Binding Sites; D002843:Chromatin / Q000235:genetics*; D003850:Deoxyribonuclease I / Q000235:genetics / Q000378:metabolism; D016762:Genes, fos; D006801:Humans; D008836:Micrococcal Nuclease / Q000235:genetics / Q000378:metabolism; D009707:Nucleosomes / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012045:Regulatory Sequences, Nucleic Acid; D016385:TATA Box; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D002843:Chromatin; D009707:Nucleosomes; D014157:Transcription Factors; D003850:Deoxyribonuclease I; D008836:Micrococcal Nuclease