Analysis of LexA binding sites and transcriptomics in response to genotoxic stress in Leptospira interrogans

We determined the effects of DNA damage caused by ultraviolet radiation on gene expression in Leptospira interrogans using DNA microarrays. These data were integrated with DNA binding in vivo of LexA1, a regulator of the DNA damage response, assessed by chromatin immunoprecipitation and massively pa...

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Main Authors: Schons-Fonseca, Luciane, da Silva, Josefa B., Milanez, Juliana S., Domingos, Renan H., Smith, Janet L., Nakaya, Helder I., Ho, Paulo L., da Costa, Renata MA, Grossman, Alan Davis
Other Authors: Massachusetts Institute of Technology. Department of Biology
Format: Article
Language:en_US
Published: Oxford University Press 2016
Online Access:http://hdl.handle.net/1721.1/101672
https://orcid.org/0000-0001-5718-5366
https://orcid.org/0000-0002-8235-7227
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author Schons-Fonseca, Luciane
da Silva, Josefa B.
Milanez, Juliana S.
Domingos, Renan H.
Smith, Janet L.
Nakaya, Helder I.
Ho, Paulo L.
da Costa, Renata MA
Grossman, Alan Davis
author2 Massachusetts Institute of Technology. Department of Biology
author_facet Massachusetts Institute of Technology. Department of Biology
Schons-Fonseca, Luciane
da Silva, Josefa B.
Milanez, Juliana S.
Domingos, Renan H.
Smith, Janet L.
Nakaya, Helder I.
Ho, Paulo L.
da Costa, Renata MA
Grossman, Alan Davis
author_sort Schons-Fonseca, Luciane
collection MIT
description We determined the effects of DNA damage caused by ultraviolet radiation on gene expression in Leptospira interrogans using DNA microarrays. These data were integrated with DNA binding in vivo of LexA1, a regulator of the DNA damage response, assessed by chromatin immunoprecipitation and massively parallel DNA sequencing (ChIP-seq). In response to DNA damage, Leptospira induced expression of genes involved in DNA metabolism, in mobile genetic elements and defective prophages. The DNA repair genes involved in removal of photo-damage (e.g. nucleotide excision repair uvrABC, recombinases recBCD and resolvases ruvABC) were not induced. Genes involved in various metabolic pathways were down regulated, including genes involved in cell growth, RNA metabolism and the tricarboxylic acid cycle. From ChIP-seq data, we observed 24 LexA1 binding sites located throughout chromosome 1 and one binding site in chromosome 2. Expression of many, but not all, genes near those sites was increased following DNA damage. Binding sites were found as far as 550 bp upstream from the start codon, or 1 kb into the coding sequence. Our findings indicate that there is a shift in gene expression following DNA damage that represses genes involved in cell growth and virulence, and induces genes involved in mutagenesis and recombination.
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spelling mit-1721.1/1016722022-09-26T11:22:42Z Analysis of LexA binding sites and transcriptomics in response to genotoxic stress in Leptospira interrogans Schons-Fonseca, Luciane da Silva, Josefa B. Milanez, Juliana S. Domingos, Renan H. Smith, Janet L. Nakaya, Helder I. Ho, Paulo L. da Costa, Renata MA Grossman, Alan Davis Massachusetts Institute of Technology. Department of Biology Schons-Fonseca, Luciane Grossman, Alan D. We determined the effects of DNA damage caused by ultraviolet radiation on gene expression in Leptospira interrogans using DNA microarrays. These data were integrated with DNA binding in vivo of LexA1, a regulator of the DNA damage response, assessed by chromatin immunoprecipitation and massively parallel DNA sequencing (ChIP-seq). In response to DNA damage, Leptospira induced expression of genes involved in DNA metabolism, in mobile genetic elements and defective prophages. The DNA repair genes involved in removal of photo-damage (e.g. nucleotide excision repair uvrABC, recombinases recBCD and resolvases ruvABC) were not induced. Genes involved in various metabolic pathways were down regulated, including genes involved in cell growth, RNA metabolism and the tricarboxylic acid cycle. From ChIP-seq data, we observed 24 LexA1 binding sites located throughout chromosome 1 and one binding site in chromosome 2. Expression of many, but not all, genes near those sites was increased following DNA damage. Binding sites were found as far as 550 bp upstream from the start codon, or 1 kb into the coding sequence. Our findings indicate that there is a shift in gene expression following DNA damage that represses genes involved in cell growth and virulence, and induces genes involved in mutagenesis and recombination. Conselho Nacional de Pesquisas (Brazil) Fundacao de Amparo a Pesquisa do Estado de Sao Paulo Fundacao Butantan National Institutes of Health (U.S.) (National Institute of General Medical Sciences (U.S.) Award GM41934) 2016-03-11T02:27:26Z 2016-03-11T02:27:26Z 2016-02 2015-12 Article http://purl.org/eprint/type/JournalArticle 0305-1048 1362-4962 http://hdl.handle.net/1721.1/101672 Schons-Fonseca, Luciane, Josefa B. da Silva, Juliana S. Milanez, Renan H. Domingos, Janet L. Smith, Helder I. Nakaya, Alan D. Grossman, Paulo L. Ho, and Renata MA da Costa. “Analysis of LexA Binding Sites and Transcriptomics in Response to Genotoxic Stress in Leptospira Interrogans.” Nucleic Acids Research 44, no. 3 (January 13, 2016): 1179–1191. https://orcid.org/0000-0001-5718-5366 https://orcid.org/0000-0002-8235-7227 en_US http://dx.doi.org/10.1093/nar/gkv1536 Nucleic Acids Research Creative Commons Attribution http://creativecommons.org/licenses/by-nc/4.0/ application/pdf Oxford University Press Oxford University Press
spellingShingle Schons-Fonseca, Luciane
da Silva, Josefa B.
Milanez, Juliana S.
Domingos, Renan H.
Smith, Janet L.
Nakaya, Helder I.
Ho, Paulo L.
da Costa, Renata MA
Grossman, Alan Davis
Analysis of LexA binding sites and transcriptomics in response to genotoxic stress in Leptospira interrogans
title Analysis of LexA binding sites and transcriptomics in response to genotoxic stress in Leptospira interrogans
title_full Analysis of LexA binding sites and transcriptomics in response to genotoxic stress in Leptospira interrogans
title_fullStr Analysis of LexA binding sites and transcriptomics in response to genotoxic stress in Leptospira interrogans
title_full_unstemmed Analysis of LexA binding sites and transcriptomics in response to genotoxic stress in Leptospira interrogans
title_short Analysis of LexA binding sites and transcriptomics in response to genotoxic stress in Leptospira interrogans
title_sort analysis of lexa binding sites and transcriptomics in response to genotoxic stress in leptospira interrogans
url http://hdl.handle.net/1721.1/101672
https://orcid.org/0000-0001-5718-5366
https://orcid.org/0000-0002-8235-7227
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