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

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-?1-42 (A?1-42) on 82-kDa ChAT disposition in SH-SY5Y neural cells, finding that acute exposure to A?1-42 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 A?1-42-exposure increases 82-kDa ChAT association with gene promoters and introns. The A?1-42-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 A?1-42 -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 A?-exposure.

SUBMITTER: Winick-Ng W 

PROVIDER: S-EPMC4823725 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature