Role of Helicase-Like Transcription Factor (Hltf) in the G2/M Transition and Apoptosis in Brain
| Autor: | Oded Foreman, Janet Dertien, Marlyn Panchoo, Beverly S. Chilton, Suhani M. Bhakta, Rebecca A. Helmer |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Chromatin Immunoprecipitation
Anatomy and Physiology Histology Genotype DNA damage DNA repair DNA transcription lcsh:Medicine Apoptosis Biology Neurological System Chromatin remodeling Gene Splicing CFLAR Molecular Genetics Mice Molecular cell biology Helicase-Like Transcription Factor Genetics Animals Protein Isoforms Gene Regulation lcsh:Science HLTF Mice Knockout Multidisciplinary Cell Death Cell Cycle lcsh:R Brain Molecular Development Cell cycle Molecular biology Signaling DNA-Binding Proteins Neuroanatomy Histone biology.protein lcsh:Q Gene expression Gene Function Animal Genetics Research Article Developmental Biology Neuroscience Transcription Factors |
| Zdroj: | PLoS ONE, Vol 8, Iss 6, p e66799 (2013) PLoS ONE |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0066799 |
| Popis: | HLTF participates in transcription, chromatin remodeling, DNA damage repair, and tumor suppression. Aside from being expressed in mouse brain during embryonic and postnatal development, little is known about Hltf's functional importance. Splice variant quantification of wild-type neonatal (6-8 hour postpartum) brain gave a ratio of 5:1 for Hltf isoform 1 (exons 1-25) to isoform 2 (exons 1-21 with exon 21 extended via a partial intron retention event). Western analysis showed a close correlation between mRNA and protein expression. Complete loss of Hltf caused encephalomalacia with increased apoptosis, and reduced viability. Sixty-four percent of Hltf null mice died, 48% within 12-24 hours of birth. An RNA-Seq snapshot of the neonatal brain transcriptome showed 341 of 20,000 transcripts were altered (p < 0.05) - 95 up regulated and 246 down regulated. MetaCoreTM enrichment pathway analysis revealed Hltf regulates cell cycle, cell adhesion, and TGF-beta receptor signaling. Hltf's most important role is in the G2/M transition of the cell cycle (p = 4.672e-7) with an emphasis on transcript availability of major components in chromosome cohesion and condensation. Hltf null brains have reduced transcript levels for Rad21/Scc1, histone H3.3, Cap-E/Smc2, Cap-G/G2, and Aurora B kinase. The loss of Hltf in its yeast Rad5-like role in DNA damage repair is accompanied by down regulation of Cflar, a critical inhibitor of TNFRSF6-mediated apoptosis, and increased (p |
| Databáze: | OpenAIRE |
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