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Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Mol+Cell 2016 ; 62 (2): 237-47 Nephropedia Template TP
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Enhancer regulation of transcriptional bursting parameters revealed by forced chromatin looping #MMPMID27067601
Bartman CR; Hsu SC; Hsiung CCS; Raj A; Blobel GA
Mol Cell 2016[Apr]; 62 (2): 237-47 PMID27067601show ga
Mammalian genes do not transcribe RNA 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 ?-globin enhancer (LCR) predominantly augments transcriptional burst fraction of the ?-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-?-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 ?-type globin genes for LCR contacts and suggest that LCR-promoter loops are formed and released with rapid kinetics.