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eRNA binding produces tailored CBP activity profiles to regulate gene expression.

Daniel A Bose1,2, Shelley L Berger3,4

  • 1a Department of Molecular Biology and Biotechnology , Sheffield Institute for Nucleic Acids, University of Sheffield, Firth Court, Western Bank , Sheffield , UK.

RNA Biology
|September 12, 2017
PubMed
Summary
This summary is machine-generated.

Enhancer RNAs (eRNAs) directly interact with Creb-binding protein (CBP), stimulating its activity. This interaction links eRNA production to histone acetylation and gene expression, revealing a novel regulatory role for eRNAs in gene regulation.

Keywords:
chromatin modificationeRNAepigenetic enzymesgene regulationnon-coding RNA

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Area of Science:

  • Molecular Biology
  • Epigenetics
  • Genetics

Background:

  • Enhancers are crucial cis-regulatory elements controlling gene expression.
  • Active enhancers produce enhancer RNAs (eRNAs) that promote gene expression.
  • The precise mechanisms by which eRNAs stimulate gene expression are not fully understood.

Purpose of the Study:

  • To investigate the interaction between eRNAs and the transcriptional co-activator Creb-binding protein (CBP).
  • To elucidate the functional role of eRNAs in modulating CBP activity and gene expression.

Main Methods:

  • Studied the direct interaction between RNAs and CBP.
  • Assessed the impact of RNA binding on CBP's histone acetyltransferase activity.
  • Linked eRNA production to CBP-dependent histone acetylation and gene expression in cells.
  • Investigated locus-specific binding of CBP to chromatin.

Main Results:

  • Demonstrated a direct interaction between RNAs and CBP.
  • Showed that RNA binding stimulates CBP's core histone acetyltransferase activity.
  • Observed a correlation between eRNA production, CBP-dependent histone acetylation, and the expression of enhancer-regulated genes.
  • Found that RNA binding to CBP is sequence-independent but locus-specific at transcribed sites where CBP is bound to chromatin.

Conclusions:

  • eRNAs function as regulatory molecules that stimulate the activity of CBP, a key epigenetic regulator.
  • eRNAs directly impact transcription by modulating the activity of chromatin-modifying enzymes and altering the chromatin environment.
  • These findings reveal a novel mechanism for gene regulation involving enhancer RNAs and epigenetic modifications.