Minor Groove Binder Distamycin Remodels Chromatin but Inhibits Transcription

Parijat Majumder; Amrita Banerjee; Jayasha Shandilya; Parijat Senapati; Snehajyoti Chatterjee; Tapas K. Kundu; Dipak Dasgupta

doi:10.1371/journal.pone.0057693

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Minor Groove Binder Distamycin Remodels Chromatin but Inhibits Transcription

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Minor Groove Binder Distamycin Remodels Chromatin but Inhibits Transcription

Parijat Majumder, Amrita Banerjee, Jayasha Shandilya, Parijat Senapati, Snehajyoti Chatterjee, Tapas K. Kundu and Dipak Dasgupta

PloS one, Vol.8(2), pp.e57693-e57693

02/27/2013

DOI: 10.1371/journal.pone.0057693

PMCID: PMC3584068

PMID: 23460895

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Abstract

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.

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Title: Subtitle: Minor Groove Binder Distamycin Remodels Chromatin but Inhibits Transcription
Creators: Parijat Majumder - Saha Institute of Nuclear Physics
Amrita Banerjee - Saha Institute of Nuclear Physics
Jayasha Shandilya - Jawaharlal Nehru Centre for Advanced Scientific Research
Parijat Senapati - Jawaharlal Nehru Centre for Advanced Scientific Research
Snehajyoti Chatterjee - Jawaharlal Nehru Centre for Advanced Scientific Research
Tapas K. Kundu - Jawaharlal Nehru Centre for Advanced Scientific Research
Dipak Dasgupta - Saha Institute of Nuclear Physics
Resource Type: Journal article
Publication Details: PloS one, Vol.8(2), pp.e57693-e57693
DOI: 10.1371/journal.pone.0057693
PMID: 23460895
PMCID: PMC3584068
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: Public Library Science
Number of pages: 9
Grant note: intramural grant MMDDA, of the Department of Atomic Energy, India
Language: English
Date published: 02/27/2013
Academic Unit: Iowa Neuroscience Institute; Neuroscience and Pharmacology
Record Identifier: 9984303853402771

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