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Transcriptional Bursting and Co-bursting Regulation by Steroid Hormone Release Pattern and Transcription Factor Mobility.

Abstract：

:Genes are transcribed in a discontinuous pattern referred to as RNA bursting, but the mechanisms regulating this process are unclear. Although many physiological signals, including glucocorticoid hormones, are pulsatile, the effects of transient stimulation on bursting are unknown. Here we characterize RNA synthesis from single-copy glucocorticoid receptor (GR)-regulated transcription sites (TSs) under pulsed (ultradian) and constant hormone stimulation. In contrast to constant stimulation, pulsed stimulation induces restricted bursting centered around the hormonal pulse. Moreover, we demonstrate that transcription factor (TF) nuclear mobility determines burst duration, whereas its bound fraction determines burst frequency. Using 3D tracking of TSs, we directly correlate TF binding and RNA synthesis at a specific promoter. Finally, we uncover a striking co-bursting pattern between TSs located at proximal and distal positions in the nucleus. Together, our data reveal a dynamic interplay between TF mobility and RNA bursting that is responsive to stimuli strength, type, modality, and duration.

journal_name

Mol Cell

journal_title

Molecular cell

authors

Stavreva DA,Garcia DA,Fettweis G,Gudla PR,Zaki GF,Soni V,McGowan A,Williams G,Huynh A,Palangat M,Schiltz RL,Johnson TA,Presman DM,Ferguson ML,Pegoraro G,Upadhyaya A,Hager GL

doi

10.1016/j.molcel.2019.06.042

subject

Has Abstract

pub_date

2019-09-19 00:00:00

pages

1161-1177.e11

issue

6

eissn

1097-2765

issn

1097-4164

pii

S1097-2765(19)30499-X

journal_volume

75

pub_type

杂志文章

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