The long non-coding RNA NEAT1 is a ΔNp63 target gene modulating epidermal differentiation

Area of Science:

• Molecular Biology
• Cell Biology
• Genetics

Background:

• The transcription factor ΔNp63 is crucial for epithelial stem cell function and stratified tissue integrity.
• Its role in regulating long non-coding RNA (lncRNA) expression, particularly NEAT1, is not well understood.

Purpose of the Study:

• To investigate the functional link between ΔNp63 transcriptional activity and NEAT1 lncRNA expression.
• To elucidate the role of NEAT1 in epidermal differentiation and morphogenesis.

Main Methods:

• Utilized human keratinocytes to study ΔNp63 and NEAT1 interactions.
• Employed techniques including RNA sequencing (RNA-seq) and Chromatin Isolation by RNA Purification sequencing (ChIRP-seq).
• Investigated the recruitment of Histone Deacetylase 1 (HDAC1) to the NEAT1 promoter.

Main Results:

• ΔNp63 represses NEAT1 expression in proliferating keratinocytes by recruiting HDAC1.
• ΔNp63 down-regulation during differentiation leads to increased NEAT1 levels and paraspeckle formation.
• NEAT1 associates with promoters of epithelial transcription factors, sustaining their expression during differentiation.
• NEAT1 depletion impairs proper epidermal layer formation in keratinocytes.

Conclusions:

• Uncovered a novel regulatory pathway where ΔNp63 controls NEAT1 expression.
• Identified NEAT1 as a key player in epidermal differentiation and morphogenesis.
• Highlights the intricate network involving lncRNAs in maintaining epithelial tissue integrity.