title: Recognition of chromatin by the plant alkaloid, ellipticine as a dual binder.
abstract: Recognition of core histone components of chromatin along with chromosomal DNA by a class of small molecule modulators is worth examining to evaluate their intracellular mode of action. A plant alkaloid ellipticine (ELP) which is a putative anticancer agent has so far been reported to function via DNA intercalation, association with topoisomerase II and binding to telomere region. However, its effect upon the potential intracellular target, chromatin is hitherto unreported. Here we have characterized the biomolecular recognition between ELP and different hierarchical levels of chromatin. The significant result is that in addition to DNA, it binds to core histone(s) and can be categorized as a 'dual binder'. As a sequel to binding with histone(s) and core octamer, it alters post-translational histone acetylation marks. We have further demonstrated that it has the potential to modulate gene expression thereby regulating several key biological processes such as nuclear organization, transcription, translation and histone modifications.
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: 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: Parijat
authors.initials: P
authors.lastname: Majumder
authors.affiliation: Bionivid Technology Pvt Ltd, Kasturi Nagar, Bangalore 560043, India.
authors.forename: Payal
authors.initials: P
authors.lastname: Chakraborty
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. Electronic address: chandrima.das@saha.ac.in.
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. Electronic address: dipak.dasgupta@saha.ac.in.
authors.forename: Dipak
authors.initials: D
authors.lastname: Dasgupta
mesh_terms: D000215:Acylation; D002843:Chromatin / Q000187:drug effects* / Q000378:metabolism; D002942:Circular Dichroism; D004611:Ellipticines / Q000494:pharmacology*; D006657:Histones / Q000378:metabolism; D011485:Protein Binding; D013050:Spectrometry, Fluorescence
chemical_list: D002843:Chromatin; D004611:Ellipticines; D006657:Histones; C034192:ellipticine
keywords: Dual binder; Ellipticine; Gene expression; Histone acetylation; Plant alkaloid