title: Extension of chromatin accessibility by nuclear matrix attachment regions.
abstract: Transcription of the variable region of the rearranged immunoglobulin mu gene is dependent on an enhancer sequence situated within one of the introns of the gene. Experiments with transgenic mice have shown that activation of the promoter controlling this transcription also requires the matrix-attachment regions (MARs) that flank the intronic enhancer. As this mu gene enhancer can establish local areas of accessible chromatin, we investigated whether the MARs can extend accessibility to more distal positions. We eliminated interactions between enhancer- and promoter-bound factors by linking mu enhancer/MAR fragments to the binding sites for bacteriophage RNA polymerases that were either close to or one kilobase distal to the enhancer. The mu enhancer alone mediated chromatin accessibility at the proximal site but required a flanking MAR to confer accessibility upon the distal promoter. This long-range accessibility correlates with extended demethylation of the gene construct but not with whether it is being actively transcribed. MARs thus collaborate with the mu enhancer to generate an extended domain of accessible chromatin.
authors.affiliation: Howard Hughes Medical Institute, University of California, San Francisco 94143-0414, USA.
authors.forename: T
authors.initials: T
authors.lastname: Jenuwein
authors.forename: W C
authors.initials: WC
authors.lastname: Forrester
authors.forename: L A
authors.initials: LA
authors.lastname: Fernández-Herrero
authors.forename: G
authors.initials: G
authors.lastname: Laible
authors.forename: M
authors.initials: M
authors.lastname: Dull
authors.forename: R
authors.initials: R
authors.lastname: Grosschedl
mesh_terms: D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D002843:Chromatin / Q000502:physiology*; D019175:DNA Methylation; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D003850:Deoxyribonuclease I; D004742:Enhancer Elements, Genetic; D007148:Immunoglobulin mu-Chains / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D015530:Nuclear Matrix / Q000502:physiology*; D012045:Regulatory Sequences, Nucleic Acid; D013604:T-Phages / Q000201:enzymology; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; D007148:Immunoglobulin mu-Chains; D012321:DNA-Directed RNA Polymerases; D003850:Deoxyribonuclease I