Journal article
Transcriptional Coactivator and Chromatin Protein PC4 Is Involved in Hippocampal Neurogenesis and Spatial Memory Extinction
The Journal of biological chemistry, Vol.291(39), pp.20303-20314
09/2016
DOI: 10.1074/jbc.M116.744169
PMCID: PMC5034031
PMID: 27471272
Abstract
Although the elaborate combination of histone and non-histone protein complexes defines chromatin organization and hence regulates numerous nuclear processes, the role of chromatin organizing proteins remains unexplored at the organismal level. The highly abundant, multifunctional, chromatin-associated protein and transcriptional coactivator positive coactivator 4 (PC4/Sub1) is absolutely critical for life, because its absence leads to embryonic lethality. Here, we report results obtained with conditional PC4 knock-out (PC4f/f Nestin-Cre) mice where PC4 is knocked out specifically in the brain. Compared with the control (PC4+/+ Nestin-Cre) mice, PC4f/f Nestin-Cre mice are smaller with decreased nocturnal activity but are fertile and show no motor dysfunction. Neurons in different areas of the brains of these mice show sensitivity to hypoxia/anoxia, and decreased adult neurogenesis was observed in the dentate gyrus. Interestingly, PC4f/f Nestin-Cre mice exhibit a severe deficit in spatial memory extinction, whereas acquisition and long term retention were unaffected. Gene expression analysis of the dorsal hippocampus of PC4f/f Nestin-Cre mice revealed dysregulated expression of several neural function-associated genes, and PC4 was consistently found to localize on the promoters of these genes, indicating that PC4 regulates their expression. These observations indicate that non-histone chromatin-associated proteins like PC4 play a significant role in neuronal plasticity.
Details
- Title: Subtitle
- Transcriptional Coactivator and Chromatin Protein PC4 Is Involved in Hippocampal Neurogenesis and Spatial Memory Extinction
- Creators
- Amrutha Swaminathan - Jawaharlal Nehru Centre for Advanced Scientific ResearchHélène Delage - École Normale Supérieure de LyonSnehajyoti Chatterjee - Laboratoire de Neurosciences Cognitives et AdaptativesLaurence Belgarbi-Dutron - École Normale Supérieure de LyonRaphaelle Cassel - Laboratoire de Neurosciences Cognitives et AdaptativesNicole Martinez - École Normale Supérieure de LyonBrigitte Cosquer - Laboratoire de Neurosciences Cognitives et AdaptativesSujata Kumari - Jawaharlal Nehru Centre for Advanced Scientific ResearchFabien Mongelard - École Normale Supérieure de LyonBéatrice Lannes - Hôpital d'HautepierreJean-Christophe Cassel - Laboratoire de Neurosciences Cognitives et AdaptativesAnne-Laurence Boutillier - Laboratoire de Neurosciences Cognitives et AdaptativesPhilippe Bouvet - École Normale Supérieure de LyonTapas K. Kundu - Jawaharlal Nehru Centre for Advanced Scientific Research
- Resource Type
- Journal article
- Publication Details
- The Journal of biological chemistry, Vol.291(39), pp.20303-20314
- DOI
- 10.1074/jbc.M116.744169
- PMID
- 27471272
- PMCID
- PMC5034031
- NLM abbreviation
- J Biol Chem
- ISSN
- 0021-9258
- eISSN
- 1083-351X
- Publisher
- Elsevier Inc
- Grant note
- French Embassy in India
- Language
- English
- Date published
- 09/2016
- Academic Unit
- Iowa Neuroscience Institute; Neuroscience and Pharmacology
- Record Identifier
- 9984303852902771
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