TY  - JOUR
AU  - Keppel, Marc
AU  - Hünnefeld, Max
AU  - Filipchyk, Andrei
AU  - Viets, Ulrike
AU  - Davoudi, Cedric-Farhad
AU  - Krüger, Aileen
AU  - Mack, Christina
AU  - Pfeifer, Eugen
AU  - Polen, Tino
AU  - Baumgart, Meike
AU  - Bott, Michael
AU  - Frunzke, Julia
TI  - HrrSA orchestrates a systemic response to heme and determines prioritization of terminal cytochrome oxidase expression
JO  - Nucleic acids research
VL  - 48
IS  - 12
SN  - 0305-1048
CY  - London
PB  - Information Retrieval Ltd.86606
M1  - FZJ-2020-02463
SP  - 6547-6562
PY  - 2020
N1  - Biotechnologie 1
AB  - Heme is a multifaceted molecule. While serving as a prosthetic group for many important proteins, elevated levels are toxic to cells. The complexity of this stimulus has shaped bacterial network evolution. However, only a small number of targets controlled by heme-responsive regulators have been described to date. Here, we performed chromatin affinity purification and sequencing to provide genome-wide insights into in vivo promoter occupancy of HrrA, the response regulator of the heme-regulated two-component system HrrSA of Corynebacterium glutamicum. Time-resolved profiling revealed dynamic binding of HrrA to more than 200 different genomic targets encoding proteins associated with heme biosynthesis, the respiratory chain, oxidative stress response and cell envelope remodeling. By repression of the extracytoplasmic function sigma factor sigC, which activates the cydABCD operon, HrrA prioritizes the expression of genes encoding the cytochrome bc1-aa3 supercomplex. This is also reflected by a significantly decreased activity of the cytochrome aa3 oxidase in the ΔhrrA mutant. Furthermore, our data reveal that HrrA also integrates the response to heme-induced oxidative stress by activating katA encoding the catalase. These data provide detailed insights in the systemic strategy that bacteria have evolved to respond to the versatile signaling molecule heme.
LB  - PUB:(DE-HGF)16
C6  - pmid:32453397
UR  - <Go to ISI:>//WOS:000574288800018
DO  - DOI:10.1093/nar/gkaa415
UR  - https://juser.fz-juelich.de/record/877824
ER  -