TY - JOUR
T1 - Long non-coding RNA uc.291 controls epithelial differentiation by interfering with the ACTL6A/BAF complex
AU - Panatta, Emanuele
AU - Lena, Anna Maria
AU - Mancini, Mara
AU - Smirnov, Artem
AU - Marini, Alberto
AU - Delli Ponti, Riccardo
AU - Botta-Orfila, Teresa
AU - Tartaglia, Gian Gaetano
AU - Mauriello, Alessandro
AU - Zhang, Xinna
AU - Calin, George A.
AU - Melino, Gerry
AU - Candi, Eleonora
N1 - Publisher Copyright:
© 2020 The Authors. Published under the terms of the CC BY NC ND 4.0 license
PY - 2020/3/4
Y1 - 2020/3/4
N2 - The mechanisms that regulate the switch between epidermal progenitor state and differentiation are not fully understood. Recent findings indicate that the chromatin remodelling BAF complex (Brg1-associated factor complex or SWI/SNF complex) and the transcription factor p63 mutually recruit one another to open chromatin during epidermal differentiation. Here, we identify a long non-coding transcript that includes an ultraconserved element, uc.291, which physically interacts with ACTL6A and modulates chromatin remodelling to allow differentiation. Loss of uc.291 expression, both in primary keratinocytes and in three-dimensional skin equivalents, inhibits differentiation as indicated by epidermal differentiation complex genes down-regulation. ChIP experiments reveal that upon uc.291 depletion, ACTL6A is bound to the differentiation gene promoters and inhibits BAF complex targeting to induce terminal differentiation genes. In the presence of uc.291, the ACTL6A inhibitory effect is released, allowing chromatin changes to promote the expression of differentiation genes. Thus, uc.291 interacts with ACTL6A to modulate chromatin remodelling activity, allowing the transcription of late differentiation genes.
AB - The mechanisms that regulate the switch between epidermal progenitor state and differentiation are not fully understood. Recent findings indicate that the chromatin remodelling BAF complex (Brg1-associated factor complex or SWI/SNF complex) and the transcription factor p63 mutually recruit one another to open chromatin during epidermal differentiation. Here, we identify a long non-coding transcript that includes an ultraconserved element, uc.291, which physically interacts with ACTL6A and modulates chromatin remodelling to allow differentiation. Loss of uc.291 expression, both in primary keratinocytes and in three-dimensional skin equivalents, inhibits differentiation as indicated by epidermal differentiation complex genes down-regulation. ChIP experiments reveal that upon uc.291 depletion, ACTL6A is bound to the differentiation gene promoters and inhibits BAF complex targeting to induce terminal differentiation genes. In the presence of uc.291, the ACTL6A inhibitory effect is released, allowing chromatin changes to promote the expression of differentiation genes. Thus, uc.291 interacts with ACTL6A to modulate chromatin remodelling activity, allowing the transcription of late differentiation genes.
KW - ACTL6A/BAF complex
KW - epidermis
KW - keratinocyte
KW - lncRNA
UR - http://www.scopus.com/inward/record.url?scp=85078920222&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85078920222&partnerID=8YFLogxK
U2 - 10.15252/embr.201846734
DO - 10.15252/embr.201846734
M3 - Article
C2 - 32017402
AN - SCOPUS:85078920222
SN - 1469-221X
VL - 21
JO - EMBO reports
JF - EMBO reports
IS - 3
M1 - e46734
ER -