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Title: Transcriptional Coactivator and Chromatin Protein PC4 Is Involved in Hippocampal Neurogenesis and Spatial Memory Extinction
Authors: Swaminathan, Amrutha
Delage, Helene
Chatterjee, Snehajyoti
Belgarbi-Dutron, Laurence
Cassel, Raphaelle
Martinez, Nicole
Cosquer, Brigitte
Kumari, Sujata
Mongelard, Fabien
Lannes, Beatrice
Cassel, Jean-Christophe
Boutillier, Anne-Laurence
Bouvet, Philippe
Kundu, Tapas Kumar
Keywords: Biochemistry & Molecular Biology
chromatin structure
gene expression
transgenic mice
Spatial memory
Medial Prefrontal Cortex
Adult Neurogenesis
Fear Extinction
Issue Date: 2016
Publisher: American Society Biochemistry Molecular Biology Inc
Citation: Swaminathan, A.; Delage, H.; Chatterjee, S.; Belgarbi-Dutron, L.; Cassel, R.; Martinez, N.; Cosquer, B.; Kumari, S.; Mongelard, F.; Lannes, B.; Cassel, J. C.; Boutillier, A. L.; Bouvet, P.; Kundu, T. K., Transcriptional Coactivator and Chromatin Protein PC4 Is Involved in Hippocampal Neurogenesis and Spatial Memory Extinction. Journal of Biological Chemistry 2016, 291 (39), 20303-20314
Journal of Biological Chemistry
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 (PC4(f/f) Nestin-Cre) mice where PC4 is knocked out specifically in the brain. Compared with the control (PC4(+/+) Nestin-Cre) mice, PC4(f/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, PC4(f/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 PC4(f/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.
Description: Restricted Access
ISSN: 0021-9258
Appears in Collections:Research Papers (Tapas K. Kundu)

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