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Functional analysis of a novel DNA binding protein of Streptomyces coelicolor. / Matthew J Aldridge

Swansea University Author: Matthew J Aldridge

Abstract

Secondary metabolism occurs after the main growth phase in Streptomyces. A 'transition phase' occurs to remodel global patterns of gene expression at the onset of physiological and developmental differentiation. Many different signals influence this transition phase, integrating, for examp...

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Published: 2012
Institution: Swansea University
Degree level: Doctoral
Degree name: Ph.D
URI: https://cronfa.swan.ac.uk/Record/cronfa42406
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spelling 2018-08-29T14:26:57.5202363 v2 42406 2018-08-02 Functional analysis of a novel DNA binding protein of Streptomyces coelicolor. 4dc63403feea9419f825e467cc1fa093 NULL Matthew J Aldridge Matthew J Aldridge true true 2018-08-02 Secondary metabolism occurs after the main growth phase in Streptomyces. A 'transition phase' occurs to remodel global patterns of gene expression at the onset of physiological and developmental differentiation. Many different signals influence this transition phase, integrating, for example, information on nutritional status, growth rate, and stress responses. Several pleiotropic transcription factors that regulate the transition phase have been identified, but aspects of epigenetic control of gene expression are not well understood. This study focused on the characterisation of a novel gene sco2075 in S. coelicolor encoding a protein that combines a histone-like domain with a conserved DksA-like domain, the latter considered a ppGpp cofactor. The protein is important for integrating responses to both oxidative and osmotic stresses. The sco2075- mutant strain is sensitive to oxidative stress at least in part due to reduced induction of the alternative sigma factor sigmaR. SCO2075, similarly to E. coli DksA, may play a possible role in the liberation of core RNA polymerase to bind alternative sigma factors such as sigmaR. In addition DSCO2075 has an altered topological profile of a reporter plasmid under osmotic stress, showing little alteration in negative supercoiling when compared to the significant increase in wildtype. DSCO2075 also has a reduction in aerial hyphae and a possible reduction in actinorhodin production when grown with osmolyte. The histone-like domain of SCO2075 binds DNA non-specifically. SCO2075 expression appears to coincide with diffused FtsZ expression prior to Z-ring formation when SCO2075 appears to become nucleoid associated. Analysis of pre-spore compartment lengths showed SCO2075 is one of several nucleoid associated proteins involved in nucleoid compaction during aerial hyphal erection and sporulation. Absence of sco2075, however, does not affect the production of unigenomic spore chains. Finally, over-expression of SCO2075 suppresses defects in secondary metabolism of a relA mutant affected in ppGpp synthesis. SCO2075 could potentially be a new type of regulator, likely acting as a node to integrate stress and physiological cues by modulating DNA topology/compaction and RNA polymerase activity. E-Thesis Genetics.;Molecular biology. 31 12 2012 2012-12-31 COLLEGE NANME Swansea University Medical School COLLEGE CODE Swansea University Doctoral Ph.D 2018-08-29T14:26:57.5202363 2018-08-02T16:24:29.1193931 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Matthew J Aldridge NULL 1 0042406-02082018162451.pdf 10798114.pdf 2018-08-02T16:24:51.8800000 Output 17790642 application/pdf E-Thesis true 2018-08-02T16:24:51.8800000 false
title Functional analysis of a novel DNA binding protein of Streptomyces coelicolor.
spellingShingle Functional analysis of a novel DNA binding protein of Streptomyces coelicolor.
Matthew J Aldridge
title_short Functional analysis of a novel DNA binding protein of Streptomyces coelicolor.
title_full Functional analysis of a novel DNA binding protein of Streptomyces coelicolor.
title_fullStr Functional analysis of a novel DNA binding protein of Streptomyces coelicolor.
title_full_unstemmed Functional analysis of a novel DNA binding protein of Streptomyces coelicolor.
title_sort Functional analysis of a novel DNA binding protein of Streptomyces coelicolor.
author_id_str_mv 4dc63403feea9419f825e467cc1fa093
author_id_fullname_str_mv 4dc63403feea9419f825e467cc1fa093_***_Matthew J Aldridge
author Matthew J Aldridge
author2 Matthew J Aldridge
format E-Thesis
publishDate 2012
institution Swansea University
college_str Faculty of Medicine, Health and Life Sciences
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hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
document_store_str 1
active_str 0
description Secondary metabolism occurs after the main growth phase in Streptomyces. A 'transition phase' occurs to remodel global patterns of gene expression at the onset of physiological and developmental differentiation. Many different signals influence this transition phase, integrating, for example, information on nutritional status, growth rate, and stress responses. Several pleiotropic transcription factors that regulate the transition phase have been identified, but aspects of epigenetic control of gene expression are not well understood. This study focused on the characterisation of a novel gene sco2075 in S. coelicolor encoding a protein that combines a histone-like domain with a conserved DksA-like domain, the latter considered a ppGpp cofactor. The protein is important for integrating responses to both oxidative and osmotic stresses. The sco2075- mutant strain is sensitive to oxidative stress at least in part due to reduced induction of the alternative sigma factor sigmaR. SCO2075, similarly to E. coli DksA, may play a possible role in the liberation of core RNA polymerase to bind alternative sigma factors such as sigmaR. In addition DSCO2075 has an altered topological profile of a reporter plasmid under osmotic stress, showing little alteration in negative supercoiling when compared to the significant increase in wildtype. DSCO2075 also has a reduction in aerial hyphae and a possible reduction in actinorhodin production when grown with osmolyte. The histone-like domain of SCO2075 binds DNA non-specifically. SCO2075 expression appears to coincide with diffused FtsZ expression prior to Z-ring formation when SCO2075 appears to become nucleoid associated. Analysis of pre-spore compartment lengths showed SCO2075 is one of several nucleoid associated proteins involved in nucleoid compaction during aerial hyphal erection and sporulation. Absence of sco2075, however, does not affect the production of unigenomic spore chains. Finally, over-expression of SCO2075 suppresses defects in secondary metabolism of a relA mutant affected in ppGpp synthesis. SCO2075 could potentially be a new type of regulator, likely acting as a node to integrate stress and physiological cues by modulating DNA topology/compaction and RNA polymerase activity.
published_date 2012-12-31T03:52:54Z
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