Affiliation:
1. Institute of Genetics, Biological Research Centre, Eötvös Loránd Research Network, 6726 Szeged, Hungary
2. Doctoral School in Biology, Faculty of Science and Informatics, University of Szeged, 6726 Szeged, Hungary
Abstract
RING1 and YY1 binding protein (RYBP) is primarily known to function as a repressor being a core component of the non-canonical polycomb repressive complexes 1 (ncPRC1s). However, several ncPRC1-independent functions of RYBP have also been described. We previously reported that RYBP is essential for mouse embryonic development and that
Rybp
null mutant embryonic stem cells cannot form contractile cardiomyocytes (CMCs)
in vitro
. We also showed that PLAGL1, a cardiac transcription factor, which is often mutated in congenital heart diseases (CHDs), is not expressed in
Rybp
-null mutant CMCs. However, the underlying mechanism of how RYBP regulates
Plagl1
expression was not revealed. Here, we demonstrate that RYBP cooperated with NKX2-5 to transcriptionally activate the
P1
and
P3
promoters of the
Plagl1
gene and that this activation is ncPRC1-independent. We also show that two non-coding RNAs residing in the
Plagl1
locus can also regulate the
Plagl1
promoters. Finally, PLAGL1 was able to activate
Tnnt2
, a gene important for contractility of CMCs in transfected HEK293 cells. Our study shows that the activation of
Plagl1
by RYBP is important for sarcomere development and contractility, and suggests that RYBP, via its regulatory functions, may contribute to the development of CHDs.
Funder
National Research, Development and Innovation Office
Subject
General Biochemistry, Genetics and Molecular Biology,Immunology,General Neuroscience
Cited by
2 articles.
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