Yulia A. Polunina

SAYP and Bap170, subunits of the SWI/SNF remodeling complex, have the ability to support enhancer-dependent transcription when artificially recruited to the promoter on a transgene. We found that the phenomenon critically depends on two subunits of the Mediator kinase module, Med12 and Med13 but does not require the two other subunits of the module (Cdk8 and CycC) or other subunits of the core part of the complex. A cooperation of the above proteins in active transcription was also observed at endogenous loci, but the contribution of the subunits to the activity of a particular gene differed in different loci. The factors SAYP/Bap170 and Med12/Med13 did not form sufficiently stable interactions in the extract, and their cooperation was apparently local at regulatory elements, the presence of SAYP and Bap170 in a locus being necessary for stable recruitment of Med12 and Med13 to the locus. In addition to the above factors, the Nelf-A protein was found to participate in the process. The cooperation of the factors, independent of enzymatic activities of the complexes they are part of, appears to be a novel mechanism that maintains promoter activity and may be used in many loci of the genome. Extended intrinsically disordered regions of the factors were assumed to sustain the mechanism.

The IMD and Toll signaling pathways in Drosophila melanogaster mediate the innate immune responses to Gram-negative and Gram-positive bacteria and fungi, respectively. Here we studied the involvement of the NF-κB transcription factor Relish, which is a mediator of the IMD pathway, in the humoral immune response to the Gram-positive bacteria Micrococcus luteus and Bacillus subtilis and the entomopathogenic fungus Metarhizium anisopliae , using D. melanogaster S2 cells as a model. Activation of Relish proteolysis was observed after S2 cell treatment with the control Gram-negative bacterium Escherichia coli . We found that M. luteus had also a noticeable effect on Relish activation, while B. subtilis and M. anisopliae effects were modest. Activation patterns of the genes encoding predominantly the IMD-pathway-dependent antimicrobial peptides (AMPs) and peptidoglycan recognition proteins (PGRPs), as well as the levels of Relish recruitment to the promoters of the genes, were found to be very similar in S2 cells treated with E. coli or M. luteus but were lower and differed in the case of B. subtilis and M. anisopliae. A Relish knockdown (KD) decreased the induction levels observed for all AMP and some PGRP genes in response to M. luteus treatment and the induction levels observed for several AMP genes after M. anisopliae and B. subtilis exposures. Therefore, our findings suggest that Relish plays a critical role in inducing the humoral immune response in Drosophila S2 cells, contributing primarily to the response against M. luteus and, to a lesser extent, to the responses against B. subtilis and M. anisopliae .

SWI/SNF protein complexes are evolutionarily conserved epigenetic regulators described in all eukaryotes. In metameric animals, the complexes are involved in all processes occurring in the nervous system, from neurogenesis to higher brain functions. On the one hand, the range of roles is wide because the SWI/SNF complexes act universally by mobilizing the nucleosomes in a chromatin template at multiple loci throughout the genome. On the other hand, the complexes mediate the action of multiple signaling pathways that control most aspects of neural tissue development and function. The issues are discussed to provide insight into the molecular basis of the multifaceted role of SWI/SNFs in cell cycle regulation, DNA repair, activation of immediate-early genes, neurogenesis, and brain and connectome formation. An overview is additionally provided for the molecular basis of nervous system pathologies associated with the SWI/SNF complexes and their contribution to neuroinflammation and neurodegeneration. Finally, we discuss the idea that SWI/SNFs act as an integration platform to connect multiple signaling and genetic programs. Graphical Abstract