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Cell Death Dis. 2014 May 29;5:e1268. doi: 10.1038/cddis.2014.228.

The cockayne syndrome B protein is essential for neuronal differentiation and neuritogenesis.

Author information

1
Unit of Molecular Genetics of Aging, Department of Ecology and Biology-University of Tuscia, 01100 Viterbo, Italy.
2
Department of Haematology, University of Cambridge, Cambridge CB2 0PT, UK.
3
Department of Radiation Oncology, Center for Radiological Research, Columbia University Medical Center, New York, NY 10032, USA.

Abstract

Cockayne syndrome (CS) is a progressive developmental and neurodegenerative disorder resulting in premature death at childhood and cells derived from CS patients display DNA repair and transcriptional defects. CS is caused by mutations in csa and csb genes, and patients with csb mutation are more prevalent. A hallmark feature of CSB patients is neurodegeneration but the precise molecular cause for this defect remains enigmatic. Further, it is not clear whether the neurodegenerative condition is due to loss of CSB-mediated functions in adult neurogenesis. In this study, we examined the role of CSB in neurogenesis by using the human neural progenitor cells that have self-renewal and differentiation capabilities. In this model system, stable CSB knockdown dramatically reduced the differentiation potential of human neural progenitor cells revealing a key role for CSB in neurogenesis. Neurite outgrowth, a characteristic feature of differentiated neurons, was also greatly abolished in CSB-suppressed cells. In corroboration with this, expression of MAP2 (microtubule-associated protein 2), a crucial player in neuritogenesis, was also impaired in CSB-suppressed cells. Consistent with reduced MAP2 expression in CSB-depleted neural cells, tandem affinity purification and chromatin immunoprecipitation studies revealed a potential role for CSB in the assembly of transcription complex on MAP2 promoter. Altogether, our data led us to conclude that CSB has a crucial role in coordinated regulation of transcription and chromatin remodeling activities that are required during neurogenesis.

PMID:
24874740
PMCID:
PMC4047889
DOI:
10.1038/cddis.2014.228
[Indexed for MEDLINE]
Free PMC Article

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