Abstract:
:The ability to regulate gene expression through transcription initiation underlies the adaptability and survival of all bacteria. Recent work has revealed that the transcription machinery in many bacteria diverges from the paradigm that has been established in Escherichia coliMycobacterium tuberculosis (Mtb) encodes the RNA polymerase (RNAP)-binding protein CarD, which is absent in E. coli but is required to form stable RNAP-promoter open complexes (RPo) and is essential for viability in Mtb The stabilization of RPo by CarD has been proposed to result in activation of gene expression; however, CarD has only been examined on limited promoters that do not represent the typical promoter structure in Mtb In this study, we investigate the outcome of CarD activity on gene expression from Mtb promoters genome-wide by performing RNA sequencing on a panel of mutants that differentially affect CarD's ability to stabilize RPo In all CarD mutants, the majority of Mtb protein encoding transcripts were differentially expressed, demonstrating that CarD had a global effect on gene expression. Contrary to the expected role of CarD as a transcriptional activator, mutation of CarD led to both up- and down-regulation of gene expression, suggesting that CarD can also act as a transcriptional repressor. Furthermore, we present evidence that stabilization of RPo by CarD could lead to transcriptional repression by inhibiting promoter escape, and the outcome of CarD activity is dependent on the intrinsic kinetic properties of a given promoter region. Collectively, our data support CarD's genome-wide role of regulating diverse transcription outcomes.
journal_name
Proc Natl Acad Sci U S Aauthors
Zhu DX,Garner AL,Galburt EA,Stallings CLdoi
10.1073/pnas.1900176116subject
Has Abstractpub_date
2019-07-02 00:00:00pages
13573-13581issue
27eissn
0027-8424issn
1091-6490pii
1900176116journal_volume
116pub_type
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