An active tissue-specific enhancer and bound transcription factors existing in a precisely positioned nucleosomal array.
Nucleosomes positioned over promoters are usually inhibitory to protein binding and activity. We analyzed at the nucleotide level of resolution the nucleosomal organization of a distal, liver-specific enhancer in various mouse tissues and found that the enhancer exists in an array of three precisely positioned nucleosomes only in liver chromatin, where the enhancer is active. In vivo footprinting reveals that essential transcription factor-binding sites are occupied on apparent nucleosome surfaces, in one case leading to a perturbed nucleosomal structure. A similar nucleosomal array is generated with an in vitro chromatin assembly system in which nucleosome positioning is dependent upon binding to the enhancer of proteins related to hepatocyte nuclear factor 3. We suggest that certain transcription factors can organize nucleosomal structures that define an active enhancer element.
McPherson
C E
CE
Section of Biochemistry, Brown University, Providence, Rhode Island 02912.
Shim
E Y
EY
Friedman
D S
DS
Zaret
K S
KS
D000818:Animals; D001483:Base Sequence; D002843:Chromatin / Q000648:ultrastructure; D015254:DNA Modification Methylases; D003850:Deoxyribonuclease I / Q000378:metabolism; D004330:Drosophila; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D008099:Liver / Q000378:metabolism / Q000648:ultrastructure*; D046911:Macromolecular Substances; D008745:Methylation; D051379:Mice; D008809:Mice, Inbred C3H; D008836:Micrococcal Nuclease / Q000378:metabolism; D008969:Molecular Sequence Data; D009068:Movement; D009707:Nucleosomes / Q000378:metabolism / Q000648:ultrastructure*; D009928:Organ Specificity; D016133:Polymerase Chain Reaction; D012709:Serum Albumin / Q000235:genetics*; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
D002843:Chromatin; D046911:Macromolecular Substances; D009707:Nucleosomes; D012709:Serum Albumin; D014157:Transcription Factors; D015254:DNA Modification Methylases; D003850:Deoxyribonuclease I; D008836:Micrococcal Nuclease