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

• DOI: 10.1016/j.bbrc.2015.04.140
• Publication Date: 2015-05-08T06:51:02Z
• Authors: Amrita Banerjee; Sulagna Sanyal; Parijat Majumder; Payal Chakraborty; Kuladip Jana; Chandrima Das; Dipak Dasgupta
• Keywords: Histone octamer; Histone code; Histone Methylation

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.