The Putative Epigenetic Reader SntB Regulates Development and Secondary Metabolism in Aspergillus spp.

Chromatin remodeling proteins are well known to regulate biosynthetic gene clusters (BGCs) by influencing the accessibility of the DNA through modifications of histone tails. The regulation of BGCs through chromatin aids in the coordinated effort to express or repress an entire co-regulated set of genes. Genetic manipulation of these epigenetic regulators represents a way to activate silent BGCs, with the goal of identifying novel bioactive natural products. In a recent forward genetic screen (1), we identified two novel transcriptional regulators of the mycotoxin sterigmatocystin BGC in Aspergillus nidulans. One of these, SntB, is a 190 kDa protein with five conserved protein domains, four of which are characterized histone tail recognition domains. Domain structure and characterization of homologs leads us to hypothesize that SntB is an epigenetic reader, part of a larger histone modifying complex which controls the expression of BGCs. The function of SntB appears to be conserved in Aspergillus spp. as it is required for production of aflatoxin in A. flavus, and regulates development in both species. By using proteomics and Chromatin Immunoprecipitation (ChIP) we identify interacting proteins, as well as monitor where the SntB complex is acting. This work describes our efforts to further characterize this protein in A. nidulans by investigating the additional BGCs that are regulated by SntB, as well understanding the manner in which SntB regulates these clusters.