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Lee, M.-K.

Publications and source records attributed to Lee, M.-K..

2 recordsLinked to original sources

Conservation and Divergence in the Asexual Sporulation Gene Regulatory Network Across a Genus of Filamentous Fungi

Asexual sporulation is fundamental to the ecology and lifestyle of filamentous fungi and can facilitate both plant and human infection. In Aspergillus, the production of asexual spores is primarily governed by the BrlA[->]AbaA[->]WetA regulatory cascade. The final step in this cascade is controlled by the WetA protein and not only governs the morphological differentiation of spores but also the production and deposition of diverse metabolites into spores. While WetA is conserved across the genus Aspergillus, the structure and degree of conservation of the wetA gene regulatory network (GRN) remains largely unknown. We carried out comparative transcriptome analyses between wetA null mutant and wild type asexual spores in three representative species spanning the diversity of the genus Aspergillus: A. nidulans, A. flavus, and A. fumigatus. We discovered that WetA regulates asexual sporulation in all three species via a negative feedback loop that represses BrlA, the cascades first step. Furthermore, ChIP-seq experiments in A. nidulans asexual spores suggest that WetA is a DNA-binding protein that interacts with a novel regulatory motif. Several global regulators known to bridge spore production and the production of secondary metabolites show species-specific regulatory patterns in our data. These results suggest that the BrlA[->]AbaA[->]WetA cascades regulatory role in cellular and chemical asexual spore development is functionally conserved, but that the wetA-associated GRN has diverged during Aspergillus evolution.

microbiology

The BAP1 deubiquitinase complex is a general transcriptional co-activator

In Drosophila, a complex consisting of Calypso and ASX catalyzes H2A deubiquitination and has been reported to act as part of the Polycomb machinery in transcriptional silencing. The mammalian homologs of these proteins (BAP1 and ASXL1/2/3, respectively), are frequently mutated in various cancer types, yet their precise functions remain unclear. Using an integrative approach based on isogenic cell lines generated with CRISPR/Cas9, we uncover an unanticipated role for BAP1 in gene activation. This function requires the assembly of an enzymatically active BAPl-associated core complex (BAP1.com) containing one of the redundant ASXL proteins. We investigated the mechanism underlying BAP1.com-mediated transcriptional regulation and show that it functions neither in synergy nor by antagonism with the Polycomb machinery. Instead, our results provide compelling evidence that BAP1.com acts as a general transcriptional co-activator.

genomics