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Sci Rep. 2016 Apr 7;6:23914. doi: 10.1038/srep23914.

82-kDa choline acetyltransferase and SATB1 localize to β-amyloid induced matrix attachment regions.

Author information

1
Department of Physiology and Pharmacology, Schulich School of Medicine &Dentistry, University of Western Ontario, London, Ontario, N6A 5C1 Canada.
2
Molecular Medicine Group, Robarts Research Institute, University of Western Ontario, London, Ontario, N6A 5C1 Canada.
3
London Health Sciences Centre, London, Ontario, N6A 5W9 Canada.
4
Department of Microbiology and Immunology, Schulich School of Medicine &Dentistry, University of Western Ontario, London, Ontario, N6A 5C1 Canada.

Abstract

The M-transcript of human choline acetyltransferase (ChAT) produces an 82-kDa protein (82-kDa ChAT) that concentrates in nuclei of cholinergic neurons. We assessed the effects of acute exposure to oligomeric amyloid-β1-42 (Aβ1-42) on 82-kDa ChAT disposition in SH-SY5Y neural cells, finding that acute exposure to Aβ1-42 results in increased association of 82-kDa ChAT with chromatin and formation of 82-kDa ChAT aggregates in nuclei. When measured by chromatin immunoprecipitation with next-generation sequencing (ChIP-seq), we identified that Aβ1-42-exposure increases 82-kDa ChAT association with gene promoters and introns. The Aβ1-42-induced 82-kDa ChAT aggregates co-localize with special AT-rich binding protein 1 (SATB1), which anchors DNA to scaffolding/matrix attachment regions (S/MARs). SATB1 had a similar genomic association as 82-kDa ChAT, with both proteins associating with synapse and cell stress genes. After Aβ1-42 -exposure, both SATB1 and 82-kDa ChAT are enriched at the same S/MAR on the APP gene, with 82-kDa ChAT expression attenuating an increase in an isoform-specific APP mRNA transcript. Finally, 82-kDa ChAT and SATB1 have patterned genomic association at regions enriched with S/MAR binding motifs. These results demonstrate that 82-kDa ChAT and SATB1 play critical roles in the response of neural cells to acute Aβ-exposure.

PMID:
27052102
PMCID:
PMC4823725
DOI:
10.1038/srep23914
[Indexed for MEDLINE]
Free PMC Article

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