Abstract
Histone-like nucleoid structuring protein (H-NS) in enterobacteria plays an important role in facilitating chromosome organization and functions as a crucial transcriptional regulator for global gene regulation. Here, we presented an observation that H-NS of Salmonella enterica serovar Typhimurium could undergo protein phosphorylation at threonine 13 residue (T13). Analysis of the H-NS wild-type protein and its T13E phosphomimetic substitute suggested that T13 phosphorylation lead to alterations of H-NS structure, thus reducing its dimerization to weaken its DNA binding affinity. Proteomic analysis revealed that H-NS phosphorylation exerts regulatory effects on a wide range of genetic loci including the PhoP/PhoQ-regulated genes. In this study, we investigated an effect of T13 phosphorylation of H-NS that rendered transcription upregulation of the PhoP/PhoQ-activated genes. A lower promoter binding of the T13 phosphorylated H-NS protein was correlated with a stronger interaction of the PhoP protein, i.e., a transcription activator and also a competitor of H-NS, to the PhoP/PhoQ-dependent promoters. Unlike depletion of H-NS which dramatically activated the PhoP/PhoQ-dependent transcription even in a PhoP/PhoQ-repressing condition, mimicking of H-NS phosphorylation caused a moderate upregulation. Wild-type H-NS protein produced heterogeneously could rescue the phenotype of T13E mutant and fully restored the PhoP/PhoQ-dependent transcription enhanced by T13 phosphorylation of H-NS to wild-type levels. Therefore, our findings uncover a strategy in S. typhimurium to fine-tune the regulatory activity of H-NS through specific protein phosphorylation and highlight a regulatory mechanism for the PhoP/PhoQ-dependent transcription via this post-translational modification.
| Original language | English (US) |
|---|---|
| Article number | 1515 |
| Journal | Frontiers in Microbiology |
| Volume | 10 |
| Issue number | JUL |
| DOIs | |
| State | Published - Jan 1 2019 |
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Keywords
- Bacterial signal transduction
- Histone-like nucleoid structuring protein (H-NS)
- Post-translational modification
- Protein threonine phosphorylation
- Transcriptional regulation
ASJC Scopus subject areas
- Microbiology
- Microbiology (medical)
Cite this
Threonine phosphorylation fine-tunes the regulatory activity of histone-like nucleoid structuring protein in Salmonella transcription. / Hu, Lizhi; Kong, Wei; Yang, Dezhi; Han, Qiangqiang; Guo, Lin; Shi, Yixin.
In: Frontiers in Microbiology, Vol. 10, No. JUL, 1515, 01.01.2019.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Threonine phosphorylation fine-tunes the regulatory activity of histone-like nucleoid structuring protein in Salmonella transcription
AU - Hu, Lizhi
AU - Kong, Wei
AU - Yang, Dezhi
AU - Han, Qiangqiang
AU - Guo, Lin
AU - Shi, Yixin
PY - 2019/1/1
Y1 - 2019/1/1
N2 - Histone-like nucleoid structuring protein (H-NS) in enterobacteria plays an important role in facilitating chromosome organization and functions as a crucial transcriptional regulator for global gene regulation. Here, we presented an observation that H-NS of Salmonella enterica serovar Typhimurium could undergo protein phosphorylation at threonine 13 residue (T13). Analysis of the H-NS wild-type protein and its T13E phosphomimetic substitute suggested that T13 phosphorylation lead to alterations of H-NS structure, thus reducing its dimerization to weaken its DNA binding affinity. Proteomic analysis revealed that H-NS phosphorylation exerts regulatory effects on a wide range of genetic loci including the PhoP/PhoQ-regulated genes. In this study, we investigated an effect of T13 phosphorylation of H-NS that rendered transcription upregulation of the PhoP/PhoQ-activated genes. A lower promoter binding of the T13 phosphorylated H-NS protein was correlated with a stronger interaction of the PhoP protein, i.e., a transcription activator and also a competitor of H-NS, to the PhoP/PhoQ-dependent promoters. Unlike depletion of H-NS which dramatically activated the PhoP/PhoQ-dependent transcription even in a PhoP/PhoQ-repressing condition, mimicking of H-NS phosphorylation caused a moderate upregulation. Wild-type H-NS protein produced heterogeneously could rescue the phenotype of T13E mutant and fully restored the PhoP/PhoQ-dependent transcription enhanced by T13 phosphorylation of H-NS to wild-type levels. Therefore, our findings uncover a strategy in S. typhimurium to fine-tune the regulatory activity of H-NS through specific protein phosphorylation and highlight a regulatory mechanism for the PhoP/PhoQ-dependent transcription via this post-translational modification.
AB - Histone-like nucleoid structuring protein (H-NS) in enterobacteria plays an important role in facilitating chromosome organization and functions as a crucial transcriptional regulator for global gene regulation. Here, we presented an observation that H-NS of Salmonella enterica serovar Typhimurium could undergo protein phosphorylation at threonine 13 residue (T13). Analysis of the H-NS wild-type protein and its T13E phosphomimetic substitute suggested that T13 phosphorylation lead to alterations of H-NS structure, thus reducing its dimerization to weaken its DNA binding affinity. Proteomic analysis revealed that H-NS phosphorylation exerts regulatory effects on a wide range of genetic loci including the PhoP/PhoQ-regulated genes. In this study, we investigated an effect of T13 phosphorylation of H-NS that rendered transcription upregulation of the PhoP/PhoQ-activated genes. A lower promoter binding of the T13 phosphorylated H-NS protein was correlated with a stronger interaction of the PhoP protein, i.e., a transcription activator and also a competitor of H-NS, to the PhoP/PhoQ-dependent promoters. Unlike depletion of H-NS which dramatically activated the PhoP/PhoQ-dependent transcription even in a PhoP/PhoQ-repressing condition, mimicking of H-NS phosphorylation caused a moderate upregulation. Wild-type H-NS protein produced heterogeneously could rescue the phenotype of T13E mutant and fully restored the PhoP/PhoQ-dependent transcription enhanced by T13 phosphorylation of H-NS to wild-type levels. Therefore, our findings uncover a strategy in S. typhimurium to fine-tune the regulatory activity of H-NS through specific protein phosphorylation and highlight a regulatory mechanism for the PhoP/PhoQ-dependent transcription via this post-translational modification.
KW - Bacterial signal transduction
KW - Histone-like nucleoid structuring protein (H-NS)
KW - Post-translational modification
KW - Protein threonine phosphorylation
KW - Transcriptional regulation
UR - http://www.scopus.com/inward/record.url?scp=85068971329&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85068971329&partnerID=8YFLogxK
U2 - 10.3389/fmicb.2019.01515
DO - 10.3389/fmicb.2019.01515
M3 - Article
AN - SCOPUS:85068971329
VL - 10
JO - Frontiers in Microbiology
JF - Frontiers in Microbiology
SN - 1664-302X
IS - JUL
M1 - 1515
ER -