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Tung SY Hong JY Walz T Moazed D Liou GG 《Cellular and molecular life sciences : CMLS》2012,69(4):641-650
In the cell, many small endogenous metabolic molecules are involved in distinct cellular functions such as modulation of chromatin
structure and regulation of gene expression. O-acetyl-ADP-ribose (AAR) is a small metabolic molecule that is generated during NAD-dependent deacetylation by Sir2. Sir2
regulates gene expression, DNA repair, and genome stability. Here, we developed a novel chromatin affinity-precipitation (ChAP)
method to detect the chromatin fragments at which small molecules interact with binding partners. We used this method to demonstrate
that AAR associated with heterochromatin. Moreover, we applied the ChAP method to whole genome tiling array chips to compare
the association of AAR and Sir2. We found that AAR and Sir2 displayed similar genomic binding patterns. Furthermore, we identified
312 potential association cluster regions of AAR. The ChAP assay may therefore be a generally useful strategy to study the
small molecule association with chromosomal regions. Our results further suggest that the small metabolic molecule AAR associates
with silent chromatin regions in a Sir2-dependent manner and provide additional support for the role of AAR in assembly of
silent chromatin. 相似文献