Comparative structural and functional characteristics of different forms of saccharomyces cerevisiae red pigment and its synthetic analogue

Structural and functional characteristics of the yeast red pigment (product of polymerization of N'-flí-D-ri-bofuranosyl)-5-aminoimadazole), isolated from adel 1 mutant cells of Saccharomyces cerevisiae, its deribosy-lated derivatives (obtained by acid hydrolysis) and its synthetic pigment analogue (product of polymerization of N'-methyl-5-aminoimadazole in vitro) has been obtained. Products of in vitro polymerization were identified using mass spectrometry. The ability of these pigments to inhibit amyloid formation using insulin fibrils was compared. The entire compounds studied were able to interact with amyloids and inhibit their growth. Electron and atomic force microscopy revealed a common feature inherent in the insulin fibrils formed in presence of these compounds - they were merged into conglomerates that were more stable and resistant to the effects of ultrasound in comparison with insulin aggregates grown without pigments. We speculate that all these compounds can cause coalescence of fibrils, partially block their loose ends and, thereby, inhibit the attachment of new monomers to growing fibril

hnRNP-K targets open chromatin in mouse embryonic stem cells in concert with multiple regulators

The transcription factor Oct4 plays a key regulatory role in the induction and maintenance of cellular pluripotency. With this paper, we show that ubiquitous and multifunctional poly(C) DNA/RNA-binding protein hnRNP-K occupies Oct4 (Pou5f1) enhancers in embryonic stem cells (ESCs) but is dispensable for the initiation, maintenance, and downregulation of Oct4 gene expression. Nevertheless, hnRNP-K has an essential cell-autonomous function in ESCs to maintain their proliferation and viability. To better understand mechanisms of hnRNP-K action in ESCs we have performed ChIP-seq analysis of genome-wide binding of hnRNP-K and identified several thousands of hnRNP-K target sites that are frequently co-occupied by pluripotency-related and common factors (Oct4, TBP, Sox2, Nanog, Otx2, etc.), as well as active histone marks. Furthermore, hnRNP-K localizes exclusively within open chromatin, implying its role in the onset and/or maintenance of this chromatin state. SIGNIFICANCE STATEMENT: In this work, the authors found that poly(C)-binding protein hnRNP-K occupy distal and proximal enhancers of the Oct4 gene via TC-elements. Genome-wide analysis revealed a lot of colocalizations of hnRNP-K with TBP, Oct4, Otx2 and active histone marks. A very intriguing aspect of the study is that hnRNP-K role expands to recruitment of the general transcription factor TBP to TATA-less genes