Abstract
BackgroundThe multisubunit SIN3 complex is a global transcriptional regulator. In Drosophila, a single Sin3A gene encodes different isoforms of SIN3, of which SIN3 187 and SIN3 220 are the major isoforms. Previous studies have demonstrated functional non-redundancy of SIN3 isoforms. The role of SIN3 isoforms in regulating distinct biological processes, however, is not well characterized.ResultsWe established a Drosophila S2 cell culture model system in which cells predominantly express either SIN3 187 or SIN3 220. To identify genomic targets of SIN3 isoforms, we performed chromatin immunoprecipitation followed by deep sequencing. Our data demonstrate that upon overexpression of SIN3 187, the level of SIN3 220 decreased and the large majority of genomic sites bound by SIN3 220 were instead bound by SIN3 187. We used RNA-seq to identify genes regulated by the expression of one isoform or the other. In S2 cells, which predominantly express SIN3 220, we found that SIN3 220 directly regulates genes involved in metabolism and cell proliferation. We also determined that SIN3 187 regulates a unique set of genes and likely modulates expression of many genes also regulated by SIN3 220. Interestingly, biological pathways enriched for genes specifically regulated by SIN3 187 strongly suggest that this isoform plays an important role during the transition from the embryonic to the larval stage of development.ConclusionThese data establish the role of SIN3 isoforms in regulating distinct biological processes. This study substantially contributes to our understanding of the complexity of gene regulation by SIN3.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-2428-5) contains supplementary material, which is available to authorized users.
Highlights
The multisubunit SIN3 complex is a global transcriptional regulator
We found that a large majority of peaks of the SIN3 isoforms localized around the transcription start sites (TSS) of genes, which suggests that both SIN3 isoforms bind the promoter regions of genes to regulate transcriptional activity (Fig. 2b)
We found 86 % of SIN3 187 peaks called overlapped with 73 % of SIN3 220 peaks, indicating that the majority of genomic sites targeted by SIN3 isoforms are common (Fig. 3b)
Summary
The multisubunit SIN3 complex is a global transcriptional regulator. In Drosophila, a single Sin3A gene encodes different isoforms of SIN3, of which SIN3 187 and SIN3 220 are the major isoforms. Histone lysine acetyltransferases (KATs) and histone deacetylases (HDACs) are key effectors conferring histone acetylation and deacetylation, respectively. These enzymes are often found in complexes where they associate with a scaffold protein and accessory factors. The accessory proteins are thought to finely tune the enzymatic activity of complexes [6]. The primary role of the SIN3 complex is to mediate gene repression, evidence of transcriptional activation promoted by SIN3 has been documented [9,10,11,12,13,14]
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