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Long non-coding RNA uc.291 controls epithelial differentiation by interfering with the ACTL6A/BAF complex

Emanuele Panatta1,2, Anna Maria Lena1, Mara Mancini3

  • 1Department of Experimental Medicine, University of Rome "Tor Vergata", Rome, Italy.

EMBO Reports
|February 5, 2020
PubMed

Insights

A novel long non-coding RNA, uc.291, is crucial for skin cell differentiation. It interacts with ACTL6A to regulate chromatin remodeling, enabling the expression of key differentiation genes.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • The transition between epidermal progenitor cells and differentiated states is complex and not fully understood.
  • The Brg1-associated factor (BAF) complex and p63 transcription factor are known to interact and open chromatin during epidermal differentiation.

Purpose of the Study:

  • To identify novel regulators of epidermal differentiation.
  • To elucidate the role of a specific long non-coding transcript, uc.291, in modulating chromatin remodeling and epidermal differentiation.

Main Methods:

  • Identification and characterization of the long non-coding transcript uc.291.
  • Investigation of uc.291 interaction with ACTL6A.
  • Chromatin immunoprecipitation (ChIP) experiments to assess BAF complex targeting.
  • Analysis of gene expression in primary keratinocytes and 3D skin equivalents with and without uc.291.

Main Results:

  • uc.291 physically interacts with ACTL6A and modulates chromatin remodeling.
  • Loss of uc.291 expression inhibits epidermal differentiation and down-regulates differentiation genes.
  • In uc.291-depleted cells, ACTL6A binds differentiation gene promoters, inhibiting BAF complex targeting.
  • uc.291 releases ACTL6A's inhibitory effect, allowing chromatin changes and expression of late differentiation genes.

Conclusions:

  • uc.291 is a critical regulator of epidermal differentiation.
  • uc.291 interacts with ACTL6A to fine-tune chromatin remodeling activity.
  • This interaction facilitates the transcription of genes essential for terminal epidermal differentiation.
Keywords:
ACTL6A/BAF complexepidermiskeratinocytelncRNA

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