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Signaling coupled epigenomic regulation of gene expression

Abstract

Inheritance of genomic information independent of the DNA sequence, the epigenetics, as well as gene transcription are profoundly shaped by serine/threonine and tyrosine signaling kinases and components of the chromatin remodeling complexes. To precisely respond to a changing external milieu, human cells efficiently translate upstream signals into post-translational modifications (PTMs) on histones and coregulators such as corepressors, coactivators, DNA-binding factors and PTM modifying enzymes. Because a protein with multiple residues for putative PTMs is expected to undergo more than one PTM in cells stimulated with growth factors, the outcome of combinational PTM codes on histones and coregulators is profoundly shaped by regulatory interplays between PTMs. The genomic functions of signaling kinases in cancer cells are manifested by the downstream effectors of cytoplasmic signaling cascades as well as translocation of the cytoplasmic signaling kinases to the nucleus. Signaling-mediated phosphorylation of histones serves as a regulatory switch for other PTMs, and connects chromatin remodeling complexes into gene transcription and gene activity. Here, we will discuss the recent advances in signaling-dependent epigenomic regulation of gene transcription using a few representative cancer-relevant serine/threonine and tyrosine kinases and their interplay with chromatin remodeling factors in cancer cells.

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Acknowledgements

We regret for not discussing the deserving work from many of our colleagues due to space limitations. Over the years, signaling and chromatin remodeling studies in Rakesh Kumar laboratory have been supported by the National Institutes of Health grants CA090970 and CA088023. M. Radhakrishna Pillai laboratory is supported by the Department of Biotechnology, Government of India. S. Deivendran is supported by a Senior Research Fellowship from the Indian Council of Medical Research (No. 3/1/3/JRF-2010/MPD).

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Kumar, R., Deivendran, S., Santhoshkumar, T. et al. Signaling coupled epigenomic regulation of gene expression. Oncogene 36, 5917–5926 (2017). https://doi.org/10.1038/onc.2017.201

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