Transcription factor dosage affects changes in higher order chromatin structure associated with activation of a heterochromatic gene

被引:109
|
作者
Lundgren, M [1 ]
Chow, CM [1 ]
Sabbattini, P [1 ]
Georgiou, A [1 ]
Minaee, S [1 ]
Dillon, N [1 ]
机构
[1] Univ London Imperial Coll Sci Technol & Med, Sch Med, Hammersmith Hosp, Clin Sci Ctr,Gene Regulat & Chromatin Grp,MRC, London W12 0NN, England
基金
英国医学研究理事会;
关键词
D O I
10.1016/S0092-8674(00)00177-X
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The mechanisms of transcriptional activation in heterochromatin were investigated by using FISH to directly visualize changes in chromatin organization during activation of a heterochromatic lambda5 transgene. A DNase I hypersensitive site was shown to relocate the transgene to the outside of the pericentromeric heterochromatin complex in the absence of transcription. Activation of transcription, which is dependent on the transcription factor EBF, occurs in a stochastic manner that resembles telomeric silencing in yeast, with the transcribed gene remaining closely associated with the heterochromatin complex. Reducing the dosage of EBF results in a reduced frequency of localization of the transgene to the outside of the heterochromatin complex and lower levels of transcription. These data provide evidence that transcription factors can initiate changes in higher order chromatin structure during the earliest stages of gene activation.
引用
收藏
页码:733 / 743
页数:11
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