title: The DNA intercalators ethidium bromide and propidium iodide also bind to core histones.
abstract: Eukaryotic DNA is compacted in the form of chromatin, in a complex with histones and other non-histone proteins. The intimate association of DNA and histones in chromatin raises the possibility that DNA-interactive small molecules may bind to chromatin-associated proteins such as histones. Employing biophysical and biochemical techniques we have characterized the interaction of a classical intercalator, ethidium bromide (EB) and its structural analogue propidium iodide (PI) with hierarchical genomic components: long chromatin, chromatosome, core octamer and chromosomal DNA. Our studies show that EB and PI affect both chromatin structure and function, inducing chromatin compaction and disruption of the integrity of the chromatosome. Calorimetric studies and fluorescence measurements of the ligands demonstrated and characterized the association of these ligands with core histones and the intact octamer in absence of DNA. The ligands affect acetylation of histone H3 at lysine 9 and acetylation of histone H4 at lysine 5 and lysine 8 ex vivo. PI alters the post-translational modifications to a greater extent than EB. This is the first report showing the dual binding (chromosomal DNA and core histones) property of a classical intercalator, EB, and its longer analogue, PI, in the context of chromatin.
authors.affiliation: Biophysics & Structural Genomics Division, Saha Institute of Nuclear Physics, Block-AF, Sector-1, Bidhan Nagar, Kolkata 700064, West Bengal, India.
authors.forename: Amrita
authors.initials: A
authors.lastname: Banerjee
authors.affiliation: Biophysics & Structural Genomics Division, Saha Institute of Nuclear Physics, Block-AF, Sector-1, Bidhan Nagar, Kolkata 700064, West Bengal, India.
authors.forename: Parijat
authors.initials: P
authors.lastname: Majumder
authors.affiliation: Biophysics & Structural Genomics Division, Saha Institute of Nuclear Physics, Block-AF, Sector-1, Bidhan Nagar, Kolkata 700064, West Bengal, India.
authors.forename: Sulagna
authors.initials: S
authors.lastname: Sanyal
authors.affiliation: Biophysics & Structural Genomics Division, Saha Institute of Nuclear Physics, Block-AF, Sector-1, Bidhan Nagar, Kolkata 700064, West Bengal, India.
authors.forename: Jasdeep
authors.initials: J
authors.lastname: Singh
authors.affiliation: Division of Molecular Medicine, Centre for Translational Animal Research, Bose Institute, P-1/12 C.I.T. Scheme VIIM, Kolkata 700054, West Bengal, India.
authors.forename: Kuladip
authors.initials: K
authors.lastname: Jana
authors.affiliation: Biophysics & Structural Genomics Division, Saha Institute of Nuclear Physics, Block-AF, Sector-1, Bidhan Nagar, Kolkata 700064, West Bengal, India.
authors.forename: Chandrima
authors.initials: C
authors.lastname: Das
authors.affiliation: Biophysics & Structural Genomics Division, Saha Institute of Nuclear Physics, Block-AF, Sector-1, Bidhan Nagar, Kolkata 700064, West Bengal, India.
authors.forename: Dipak
authors.initials: D
authors.lastname: Dasgupta
keywords: Chromatin compaction; DLS, dynamic light scattering; DNA release; EB, ethidium bromide; HAT, histone acetyl transferase; HMG, high mobility group; Histone acetylation; Histone and DNA binding; ITC, isothermal titration calorimetry; MTT, (3-(4-5 dimethylthiozol-2-yl) 2-5diphenyl-tetrazolium bromide); Oct, octamer; PI, propidium iodide