TY  - JOUR
A1  - Correia Santos, Sara
A1  - Bischler, Thorsten
A1  - Westermann, Alexander J.
A1  - Vogel, Jörg
T1  - MAPS integrates regulation of actin-targeting effector SteC into the virulence control network of Salmonella small RNA PinT
JF  - Cell Reports
N2  - A full understanding of the contribution of small RNAs (sRNAs) to bacterial virulence demands knowledge of their target suites under infection-relevant conditions. Here, we take an integrative approach to capturing targets of the Hfq-associated sRNA PinT, a known post-transcriptional timer of the two major virulence programs of Salmonella enterica. Using MS2 affinity purification and RNA sequencing (MAPS), we identify PinT ligands in bacteria under in vitro conditions mimicking specific stages of the infection cycle and in bacteria growing inside macrophages. This reveals PinT-mediated translational inhibition of the secreted effector kinase SteC, which had gone unnoticed in previous target searches. Using genetic, biochemical, and microscopic assays, we provide evidence for PinT-mediated repression of steC mRNA, eventually delaying actin rearrangements in infected host cells. Our findings support the role of PinT as a central post-transcriptional regulator in Salmonella virulence and illustrate the need for complementary methods to reveal the full target suites of sRNAs.
KW  - gene expression
KW  - nondocing RNA
KW  - chaperone HFQ
KW  - soluble-RNA
KW  - SEQ
KW  - interactome
KW  - repression
KW  - secretion
KW  - infection
KW  - biology
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-259134
VL  - 34
IS  - 5
ER  - 
TY  - JOUR
A1  - Czimmerer, Zsolt
A1  - Daniel, Bence
A1  - Horvath, Attila
A1  - Rückerl, Dominik
A1  - Nagy, Gergely
A1  - Kiss, Mate
A1  - Peloquin, Matthew
A1  - Budai, Marietta M.
A1  - Cuaranta-Monroy, Ixchelt
A1  - Simandi, Zoltan
A1  - Steiner, Laszlo
A1  - Nagy Jr., Bela
A1  - Poliska, Szilard
A1  - Banko, Csaba
A1  - Bacso, Zsolt
A1  - Schulman, Ira G.
A1  - Sauer, Sascha
A1  - Deleuze, Jean-Francois
A1  - Allen, Judith E.
A1  - Benko, Szilvia
A1  - Nagy, Laszlo
T1  - The Transcription Factor STAT6 Mediates Direct Repression of Inflammatory Enhancers and Limits Activation of Alternatively Polarized Macrophages
JF  - Immunity
N2  - The molecular basis of signal-dependent transcriptional activation has been extensively studied in macrophage polarization, but our understanding remains limited regarding the molecular determinants of repression. Here we show that IL-4-activated STAT6 transcription factor is required for the direct transcriptional repression of a large number of genes during in vitro and in vivo alternative macrophage polarization. Repression results in decreased lineage-determining transcription factor, p300, and RNA polymerase II binding followed by reduced enhancer RNA expression, H3K27 acetylation, and chromatin accessibility. The repressor function of STAT6 is HDAC3 dependent on a subset of IL-4-repressed genes. In addition, STAT6-repressed enhancers show extensive overlap with the NF-κB p65 cistrome and exhibit decreased responsiveness to lipopolysaccharide after IL-4 stimulus on a subset of genes. As a consequence, macrophages exhibit diminished inflammasome activation, decreased IL-1β production, and pyroptosis. Thus, the IL-4-STAT6 signaling pathway establishes an alternative polarization-specific epigenenomic signature resulting in dampened macrophage responsiveness to inflammatory stimuli.
KW  - IL-4
KW  - STAT6
KW  - alternative macrophage polarization
KW  - transcription
KW  - repression
KW  - inflammation
KW  - inflammasome activation
KW  - pyroptosis
KW  - IL-1β
KW  - macrophage epigenomics
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-223380
VL  - 48
ER  -