Dynamic Signatures of the Epigenome: Friend or Foe?

Abstract

Highly dynamic epigenetic signaling is influenced mainly by (micro)environmental stimuli and genetic factors. The exact mechanisms affecting particular epigenomic patterns differ dependently on the context. In the current review, we focus on the causes and effects of the dynamic signatures of the human epigenome as evaluated with the high-throughput profiling data and single-gene approaches. We will discuss three different aspects of phenotypic outcomes occurring as a consequence of epigenetics interplaying with genotype and environment. The first issue is related to the cases of environmental impacts on epigenetic profile, and its adverse and advantageous effects related to human health and evolutionary adaptation. The next topic will present a model of the interwoven co-evolution of genetic and epigenetic patterns exemplified with transposable elements (TEs) and their epigenetic repressors Krüppel-associated box zinc finger proteins (KRAB–ZNFs). The third aspect concentrates on the mitosis-based microevolution that takes place during carcinogenesis, leading to clonal diversity and expansion of tumor cells. The whole picture of epigenome plasticity and its role in distinct biological processes is still incomplete. However, accumulating data define epigenomic dynamics as an essential co-factor driving adaptation at the cellular and inter-species levels with a benefit or disadvantage to the host.

Cancer evolution: Darwin and beyond

“…Those initial discoveries were substantiated by several groups with orthogonal techniques, which provided evidence for intratumour diversity across multiple cancer types (Shapiro et al , 1981 ; Teixeira et al , 1996 ; Takahashi et al , 1998 ; Maley et al , 2006 ; Cottu et al , 2008 ). However, it was only with the recent technological innovations (see Box 2), particularly next‐generation sequencing (NGS), that the full breath of ITH could start to be fully resolved (Campbell et al , 2010 ; Navin et al , 2010 ; Gerlinger et al , 2012 ; Nik‐Zainal et al , 2012b ; Walter et al , 2012 ; Patel et al , 2014 ; Sottoriva et al , 2015 ; Jamal‐Hanjani et al , 2017 ; Naxerova et al , 2017 ; Turajlic et al , 2018 ; Fittall & Van Loo, 2019 ; Rambow et al , 2019 ; Reiter et al , 2019 ; Gerstung et al , 2020 ; Machnik & Oleksiewicz, 2020 ; Marine et al , 2020 ).…”

A Paradigm Revolution or Just Better Resolution—Will Newly Emerging Superresolution Techniques Identify Chromatin Architecture as a Key Factor in Radiation-Induced DNA Damage and Repair Regulation?

“…However, due to its extensive architectural rearrangement during repair, irradiated heterochromatin may be especially prone to not only mutations but also epimutations, i.e., permanent epigenetic/structural alterations at damage sites with functional consequences [57,[180][181][182][183]. The risk of epimutations can be expected to correlate with the architecture of damaged chromatin domains rather than the physical parameters of the incident radiation; however, this phenomenon remains to be studied.…”

KRAB-ZFP Transcriptional Regulators Acting as Oncogenes and Tumor Suppressors: An Overview

“…However, to facilitate an exact transcriptomic control required for further differentiation, these TEs become restricted by their cognate KRAB-ZFPs [ 52 ]. Therefore, tight regulation of TE epigenetic status is essential for appropriate development and cell homeostasis, whereas any dysregulation may lead to aberrant differentiation and various pathologic processes, including carcinogenesis [ 26 , 45 , 53 , 54 ]. Of note, KAP1-mediated retroelement repression may be hampered due to its inefficient ribosylation.…”