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Investigating the structural features of chromodomain proteins in the human genome and predictive impacts of their mutations in cancers

Dahiya, Rashmi, Naqvi, Ahmad Abu Turab, Mohammad, Taj, Alajmi, Mohamed F., Rehman, Md. Tabish, Hussain, Afzal, Hassan, Md. Imtaiyaz
International journal of biological macromolecules 2019 v.131 pp. 1101-1116
chromatin, epigenetics, genome, histones, humans, lysine, methylation, mutation, neoplasms, therapeutics, transcription (genetics)
Epigenetic readers are specific proteins which recognize histone marks and represents the underlying mechanism for chromatin regulation. Histone H3 lysine methylation is a potential epigenetic code for the chromatin organization and transcriptional control. Recognition of histone methylation is achieved by evolutionary conserved reader modules known as chromodomain, identified in several proteins, and is involved in transcriptional silencing and chromatin remodelling. Genetic perturbations within the structurally conserved chromodomain could potentially mistarget the reader protein and impair their regulatory pathways, ultimately leading to cellular chaos by setting the stage for tumor development and progression. Here, we report the structural conservations associated with diverse functions, prognostic significance and functional consequences of mutations within chromodomain of human proteins in distinct cancers. We have extensively analysed chromodomain containing human proteins in terms of their structural-functional ability to act as a molecular switch in the recognition of methyl-lysine recognition. We further investigated the combinatorial potential, target promiscuity and binding specificity associated with their underlying mechanisms. Indeed, the molecular mechanism of epigenetic silencing significantly underlies a newer cancer therapy approach. We hope that a critical understanding of chromodomains will pave the way for novel paths of research providing newer insights into the designing of effective anti-cancer therapies.