Minor groove binder distamycin remodels chromatin but inhibits transcription.

The condensed structure of chromatin limits access of cellular machinery towards template DNA. This in turn represses essential processes like transcription, replication, repair and recombination. The repression is alleviated by a variety of energy dependent processes, collectively known as "ch...

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Autores principales:	Parijat Majumder, Amrita Banerjee, Jayasha Shandilya, Parijat Senapati, Snehajyoti Chatterjee, Tapas K Kundu, Dipak Dasgupta
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/65891f43981448aaae46fff8dee0b8a7
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spelling	oai:doaj.org-article:65891f43981448aaae46fff8dee0b8a72021-11-18T07:55:45ZMinor groove binder distamycin remodels chromatin but inhibits transcription.1932-620310.1371/journal.pone.0057693https://doaj.org/article/65891f43981448aaae46fff8dee0b8a72013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23460895/?tool=EBIhttps://doaj.org/toc/1932-6203The condensed structure of chromatin limits access of cellular machinery towards template DNA. This in turn represses essential processes like transcription, replication, repair and recombination. The repression is alleviated by a variety of energy dependent processes, collectively known as "chromatin remodeling". In a eukaryotic cell, a fine balance between condensed and de-condensed states of chromatin helps to maintain an optimum level of gene expression. DNA binding small molecules have the potential to perturb such equilibrium. We present herein the study of an oligopeptide antibiotic distamycin, which binds to the minor groove of B-DNA. Chromatin mobility assays and circular dichroism spectroscopy have been employed to study the effect of distamycin on chromatosomes, isolated from the liver of Sprague-Dawley rats. Our results show that distamycin is capable of remodeling both chromatosomes and reconstituted nucleosomes, and the remodeling takes place in an ATP-independent manner. Binding of distamycin to the linker and nucleosomal DNA culminates in eviction of the linker histone and the formation of a population of off-centered nucleosomes. This hints at a possible corkscrew type motion of the DNA with respect to the histone octamer. Our results indicate that distamycin in spite of remodeling chromatin, inhibits transcription from both DNA and chromatin templates. Therefore, the DNA that is made accessible due to remodeling is either structurally incompetent for transcription, or bound distamycin poses a roadblock for the transcription machinery to advance.Parijat MajumderAmrita BanerjeeJayasha ShandilyaParijat SenapatiSnehajyoti ChatterjeeTapas K KunduDipak DasguptaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 2, p e57693 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Parijat Majumder Amrita Banerjee Jayasha Shandilya Parijat Senapati Snehajyoti Chatterjee Tapas K Kundu Dipak Dasgupta Minor groove binder distamycin remodels chromatin but inhibits transcription.
description	The condensed structure of chromatin limits access of cellular machinery towards template DNA. This in turn represses essential processes like transcription, replication, repair and recombination. The repression is alleviated by a variety of energy dependent processes, collectively known as "chromatin remodeling". In a eukaryotic cell, a fine balance between condensed and de-condensed states of chromatin helps to maintain an optimum level of gene expression. DNA binding small molecules have the potential to perturb such equilibrium. We present herein the study of an oligopeptide antibiotic distamycin, which binds to the minor groove of B-DNA. Chromatin mobility assays and circular dichroism spectroscopy have been employed to study the effect of distamycin on chromatosomes, isolated from the liver of Sprague-Dawley rats. Our results show that distamycin is capable of remodeling both chromatosomes and reconstituted nucleosomes, and the remodeling takes place in an ATP-independent manner. Binding of distamycin to the linker and nucleosomal DNA culminates in eviction of the linker histone and the formation of a population of off-centered nucleosomes. This hints at a possible corkscrew type motion of the DNA with respect to the histone octamer. Our results indicate that distamycin in spite of remodeling chromatin, inhibits transcription from both DNA and chromatin templates. Therefore, the DNA that is made accessible due to remodeling is either structurally incompetent for transcription, or bound distamycin poses a roadblock for the transcription machinery to advance.
format	article
author	Parijat Majumder Amrita Banerjee Jayasha Shandilya Parijat Senapati Snehajyoti Chatterjee Tapas K Kundu Dipak Dasgupta
author_facet	Parijat Majumder Amrita Banerjee Jayasha Shandilya Parijat Senapati Snehajyoti Chatterjee Tapas K Kundu Dipak Dasgupta
author_sort	Parijat Majumder
title	Minor groove binder distamycin remodels chromatin but inhibits transcription.
title_short	Minor groove binder distamycin remodels chromatin but inhibits transcription.
title_full	Minor groove binder distamycin remodels chromatin but inhibits transcription.
title_fullStr	Minor groove binder distamycin remodels chromatin but inhibits transcription.
title_full_unstemmed	Minor groove binder distamycin remodels chromatin but inhibits transcription.
title_sort	minor groove binder distamycin remodels chromatin but inhibits transcription.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/65891f43981448aaae46fff8dee0b8a7
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Minor groove binder distamycin remodels chromatin but inhibits transcription.

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