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Biochem Biophys Res Commun. 2015 Jul 10;462(4):352-7. doi: 10.1016/j.bbrc.2015.04.140. Epub 2015 May 8.

Recognition of chromatin by the plant alkaloid, ellipticine as a dual binder.

Author information

1
Biophysics & Structural Genomics Division, Saha Institute of Nuclear Physics, Block-AF, Sector-1, Bidhan Nagar, Kolkata 700064, West Bengal, India.
2
Bionivid Technology Pvt Ltd, Kasturi Nagar, Bangalore 560043, India.
3
Division of Molecular Medicine, Centre for Translational Animal Research, Bose Institute, P-1/12 C.I.T. Scheme VIIM, Kolkata 700054, West Bengal, India.
4
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.
5
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.

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.

KEYWORDS:

Dual binder; Ellipticine; Gene expression; Histone acetylation; Plant alkaloid

PMID:
25960297
DOI:
10.1016/j.bbrc.2015.04.140
[Indexed for MEDLINE]

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