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Dynamic acetylation profile during mammalian neurulation

Authors :
Laura Avagliano
Sandra C. P. De Castro
Serena Cuttin
Gaetano Bulfamante
Valentina Massa
Andrew J. Copp
Patrizia Vergani
Patrizia Doi
Dawn Savery
Chiara Parodi
Nicholas D. E. Greene
Paolo Grazioli
Massa, V
Avagliano, L
Grazioli, P
De Castro, S
Parodi, C
Savery, D
Vergani, P
Cuttin, S
Doi, P
Bulfamante, G
Copp, A
Greene, N
Source :
Birth Defects Research
Publication Year :
2019
Publisher :
Wiley, 2019.

Abstract

Background Neural tube defects (NTDs) result from failure of neural tube closure during embryogenesis. These severe birth defects of the central nervous system include anencephaly and spina bifida, and affect 0.5–2 per 1,000 pregnancies worldwide in humans. It has been demonstrated that acetylation plays a pivotal role during neural tube closure, as animal models for defective histone acetyltransferase proteins display NTDs. Acetylation represents an important component of the complex network of posttranslational regulatory interactions, suggesting a possible fundamental role during primary neurulation events. This study aimed to assess protein acetylation contribution to early patterning of the central nervous system both in human and murine specimens. Methods We used both human and mouse (Cited2 −/−) samples to analyze the dynamic acetylation of proteins during embryo development through immunohistochemistry, western blot analysis and quantitative polymerase chain reaction. Results We report the dynamic profile of histone and protein acetylation status during neural tube closure. We also report a rescue effect in an animal model by chemical p53 inhibition. Conclusions Our data suggest that the p53‐acetylation equilibrium may play a role in primary neurulation in mammals.

Details

ISSN :
24721727
Volume :
112
Database :
OpenAIRE
Journal :
Birth Defects Research
Accession number :
edsair.doi.dedup.....f78af568ab12d29b27d14468fd9d04da