CoRest1 regulates neurogenesis in a stage-dependent manner
- Monestime, C.M., Taibi, A., Gates, K.P., Jiang, K., Sirotkin, H.I.
- Developmental dynamics : an official publication of the American Association of Anatomists 248(10): 918-930 (Journal)
- Registered Authors
- Gates, Keith, Sirotkin, Howard
- CoRest1, Rest/NRSF, neurogenesis, zebrafish
- MeSH Terms
- Co-Repressor Proteins/genetics
- Co-Repressor Proteins/physiology*
- Embryo, Nonmammalian
- Gene Expression Regulation, Developmental
- Mutant Proteins
- Neurogenesis/drug effects*
- Repressor Proteins/metabolism
- Sin3 Histone Deacetylase and Corepressor Complex/metabolism
- 31301200 Full text @ Dev. Dyn.
Monestime, C.M., Taibi, A., Gates, K.P., Jiang, K., Sirotkin, H.I. (2019) CoRest1 regulates neurogenesis in a stage-dependent manner. Developmental dynamics : an official publication of the American Association of Anatomists. 248(10):918-930.
Background Developmental processes, including neuronal differentiation, require precise regulation of transcription. The RE-1 silencing transcription factor (Rest), is often called a "master neuronal regulator" due to its large number of neural-specific targets. Rest recruits CoRest (Rcor) and Sin3 co-repressor complexes to gene regulatory sequences. CoRest not only associates with Rest, but with other transcription regulators. In this study, we generated zebrafish rcor1 mutants using transcription activator- like effector nucleases (TALENs), to study its requisite role in repression of Rest target genes as well as Rest-independent Rcor1 developmental functions.
Results While rcor1 mutants have a slight decrease in fitness, most survived and produced viable offspring. We examined expression levels of RE1-containing genes in Maternal Zygotic rcor1 mutants (MZrcor1) and found that Rcor1 is generally not required for repression of Rest target genes at early stages. However, MZrcor1 mutants undergo more rapid neurogenesis compared to controls. We found that at gastrula stages, Rcor1 acts as a repressor of her gene family, but at later stages, many of these genes were increased in the MZrcor1 mutant.
Conclusions Based on these findings, the central role of CoRest1 in neurogenesis is likely due to a Rest- independent role rather than as a Rest co-repressor. This article is protected by copyright. All rights reserved.
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes