Enhancer Regulation of Transcriptional Bursting Parameters Revealed by Forced Chromatin Looping

被引：251

作者：

Bartman, Caroline R. ^{[1
,2
]}

Hsu, Sarah C. ^{[1
,2
]}

Hsiung, Chris C. -S. ^{[1
,2
]}

Raj, Arjun ^{[3
]}

Blobel, Gerd A. ^{[1
,2
]}

机构：

[1] Childrens Hosp, Div Hematol, Philadelphia, PA 19104 USA

[2] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA

[3] Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USA

来源：

MOLECULAR CELL | 2016年 / 62卷 / 02期

基金：

美国国家科学基金会;

关键词：

BETA-GLOBIN LOCUS; HISTONE ACETYLATION PATTERN; STOCHASTIC GENE-EXPRESSION; CONTROL REGION; IN-VIVO; FACTOR GATA-1; ERYTHROID-DIFFERENTIATION; DEVELOPMENTAL CONTROL; HYPERSENSITIVE SITES; NUCLEAR-LOCALIZATION;

D O I：

10.1016/j.molcel.2016.03.007

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：

Mammalian genes transcribe RNA not continuously, but in bursts. Transcriptional output can be modulated by altering burst fraction or burst size, but how regulatory elements control bursting parameters remains unclear. Single-molecule RNA FISH experiments revealed that the beta-globin enhancer (LCR) predominantly augments transcriptional burst fraction of the beta-globin gene with modest stimulation of burst size. To specifically measure the impact of long-range chromatin contacts on transcriptional bursting, we forced an LCR-beta-globin promoter chromatin loop. We observed that raising contact frequencies increases burst fraction but not burst size. In cells in which two developmentally distinct LCR-regulated globin genes are cotranscribed in cis, burst sizes of both genes are comparable. However, allelic co-transcription of both genes is statistically disfavored, suggesting mutually exclusive LCR-gene contacts. These results are consistent with competition between the beta-type globin genes for LCR contacts and suggest that LCR-promoter loops are formed and released with rapid kinetics.

引用

页码：237 / 247

页数：11

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