title: Heterochromatin effects on the frequency and duration of LCR-mediated gene transcription.
abstract: Locus control regions (LCRs) are responsible for initiating and maintaining a stable tissue-specific open chromatin structure of a locus. In transgenic mice, LCRs confer high level expression on linked genes independent of position in the mouse genome. Here we show that an incomplete LCR loses this property when integrated into heterochromatic regions. Two disruption mechanisms were observed. One is classical position-effect variegation, resulting in continuous transcription in a clonal subpopulation of cells. The other is a novel mechanism resulting in intermittent gene transcription in all cells. We conclude that only a complete LCR fully overcomes heterochromatin silencing and that it controls the level of transcription by ensuring activity in all cells at all times rather than directly controlling the rate of transcription.
authors.affiliation: Erasmus University, Department of Cell Biology, Rotterdam, The Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: Milot
authors.forename: J
authors.initials: J
authors.lastname: Strouboulis
authors.forename: T
authors.initials: T
authors.lastname: Trimborn
authors.forename: M
authors.initials: M
authors.lastname: Wijgerde
authors.forename: E
authors.initials: E
authors.lastname: de Boer
authors.forename: A
authors.initials: A
authors.lastname: Langeveld
authors.forename: K
authors.initials: K
authors.lastname: Tan-Un
authors.forename: W
authors.initials: W
authors.lastname: Vergeer
authors.forename: N
authors.initials: N
authors.lastname: Yannoutsos
authors.forename: F
authors.initials: F
authors.lastname: Grosveld
authors.forename: P
authors.initials: P
authors.lastname: Fraser
mesh_terms: D000818:Animals; D002503:Centromere / Q000235:genetics; D002874:Chromosome Mapping; D003850:Deoxyribonuclease I; D015252:Deoxyribonucleases, Type II Site-Specific; D004912:Erythrocytes / Q000737:chemistry; D018628:Gene Dosage; D005786:Gene Expression Regulation / Q000235:genetics*; D005914:Globins / Q000235:genetics; D006570:Heterochromatin / Q000235:genetics*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000032:analysis; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D017384:Sequence Deletion; D015719:Single-Strand Specific DNA and RNA Endonucleases; D013997:Time Factors; D014158:Transcription, Genetic / Q000235:genetics*; D019076:Transgenes / Q000235:genetics
chemical_list: D006570:Heterochromatin; D012333:RNA, Messenger; D005914:Globins; D003850:Deoxyribonuclease I; D015252:Deoxyribonucleases, Type II Site-Specific; C056435:GTGCAC-specific type II deoxyribonucleases; D015719:Single-Strand Specific DNA and RNA Endonucleases