Polycomb PRC2 complex mediates epigenetic silencing of a critical osteogenic master regulator in the hippocampus
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2016-08
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Facultad/escuela
Idioma
en
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Elsevier B.V.
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Licencia CC
Resumen
During hippocampal neuron differentiation, the expression of critical inducers of non-neuronal cell lineages must
be efficiently silenced. Runx2 transcription factor is the master regulator of mesenchymal cells responsible for
intramembranous osteoblast differentiation and formation of the craniofacial bone tissue that surrounds and
protects the central nervous system (CNS) in mammalian embryos. The molecular mechanisms that mediate
silencing of the Runx2 gene and its downstream target osteogenic-related genes in neuronal cells have not
been explored. Here, we assess the epigenetic mechanisms that mediate silencing of osteoblast-specific genes
in CNS neurons. In particular, we address the contribution of histone epigenetic marks and histone modifiers
on the silencing of the Runx2/p57 bone-related isoform in rat hippocampal tissues at embryonic to adult stages.
Our results indicate enrichment of repressive chromatin histone marks and of the Polycomb PRC2 complex at
the Runx2/p57 promoter region. Knockdown of PRC2 H3K27-methyltransferases Ezh2 and Ezh1, or forced expres sion of the Trithorax/COMPASS subunit Wdr5 activates Runx2/p57 mRNA expression in both immature and mature
hippocampal cells. Together these results indicate that complementary epigenetic mechanisms progressively and
efficiently silence critical osteoblastic genes during hippocampal neuron differentiation.
© 2016 Elsevier B.V. All rights reserved.
Acknowledgements This work was supported by grants from FONDAP 15090007 (to M.M. and M.L.A.), FONDECYT 1130706 (to M.M.), FONDECYT 3150694 (to MS) and FONDECYT 1140301 (to B.vZ.). Additional funding was pro vided by NIH (R01 AR049069 to A.J.vW.). R.A. and F.B. were supported by Doctoral Fellowships from CONICYT, Chile. A.R. was partially funded by Doctoral Fellowships from COLCIENCIAS and Pontificia Universidad Javeriana, Colombia.
Acknowledgements This work was supported by grants from FONDAP 15090007 (to M.M. and M.L.A.), FONDECYT 1130706 (to M.M.), FONDECYT 3150694 (to MS) and FONDECYT 1140301 (to B.vZ.). Additional funding was pro vided by NIH (R01 AR049069 to A.J.vW.). R.A. and F.B. were supported by Doctoral Fellowships from CONICYT, Chile. A.R. was partially funded by Doctoral Fellowships from COLCIENCIAS and Pontificia Universidad Javeriana, Colombia.
Notas
Indexación: Scopus.
Palabras clave
Runx2, Epigenetic Regulation of Gene Expression, Hippocampus
Citación
Biochimica et Biophysica Acta - Gene Regulatory Mechanisms. Volume 1859, Issue 8, Pages 1043 - 1055. 1 August 2016
DOI
10.1016/j.bbagrm.2016.05.009