Exploring Epigenetic Mechanisms and Aberrant Reprogramming in Cancer

This report provides a detailed overview of the role of epigenetics in cancer development and progression. It begins by defining epigenetics and its importance in mammalian development, highlighting the stability and integrity of epigenetic structures. The report then delves into specific epigenetic mechanisms, including DNA methylation, histone modifications, nucleosome positioning, and the function of micro-RNAs. It discusses how these mechanisms are altered in cancer, leading to aberrant reprogramming of the epigenome. Key topics include changes in histone modifications, DNA methylation abnormalities, and epigenetic switching in cancer. The report concludes by emphasizing the significance of epigenetics in cancer research and the potential for improved treatment interventions through a better understanding of the epigenetic-cancer association. Desklib offers a wealth of resources, including past papers and solved assignments, to further support students in their studies.

Epigenetics and
Cancer
Presented By:

OUTLI
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1.0 Introduction
2.0 Epigenetic mechanisms in Cancer
 DNA Methylation
 Histone Modification
 Nucleosome positioning
 Micro-RNAs
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OUTLINE…
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3.0 Aberrant reprogramming of the epigenome
in cancer
 Changes in histone modifications in cancer
 DNA methylation abnormalities in cancer
 Epigenetic switching in cancer
Conclusion
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Introduction
 Epigenetic programming is important in the development
of mammals, and constant inheritance of epigenetic
structures (Verhoeven et al., 2016).
 Most of differentiation processes- activated and
maintained by epigenetics
 Thus marked by high level of stability and integrity
 Due to numerous interlocking response mechanisms
 Cancer-the expression of both epigenetic and genetic
alterations (Hatano et al., 2015)

Introduction…
Definition: Epigenetics
 Inherited alterations in gene manifestation activity and
manifestation that takes place without making modifying
the DNA sequences (Januar et al., 2015).
 Procedures involved in epigenetic control:
 DNA methylation,
 alterations in chromatin,
 physical alterations (nucleosome positioning), and
 micro-RNAs (Matzke and Mosher, 2014).

Literature Review :Epigenetic
mechanisms in Cancer
DNA methylation
 Significant element of the epigenetic process in
controlling gene manifestation and co-operating
with nucleosomes that regulate DNA packaging
influencing all the domains of DNA (Delpu et al.,
2013).
 Significant in the formation of 5-methylcytosine
(Smith and Meissner, 2013).
 DNMTs enzymes catalyse the alterations that occur
at 5-methylcytosine.

Literature Review :Epigenetic mechanisms
in Cancer…
DNA methylation…
 Types of DNMTs: DNMT1, DNMT3a, and DNMT3b
(Horvath, 2013).
 DNMT1 - protects the available methylation arrays after
DNA imitation
 DNMT3a & DNMT3b start methylation by targeting
unmethylated CpGs
 Expressions occur during embryogenesis
 least manifested in adult tissues (Johnson et al., 2012)
 Mechanisms are substantially modified in cancer due to
LOI (Jeltsch and Jurkowska, 2014).

Literature Review :Epigenetic mechanisms
in Cancer…
Histone modifications
 Made up of the nucleosome core that has a globular C-
terminal area and the N- terminal tail that is not
structured (Deindl et al., 2013).
 N-terminal tails of the histones go through several
posttranslational covalent alterations
 Alterations responsible for the regulation of the cellular
process such as imitation, transcription and restoration
(Zentner and Henikoff, 2013).

Literature Review :Epigenetic mechanisms
in Cancer…
Histone modifications…
 Epigenetic memory in a cell; ‘histocode’, regulates the
organization and function of varying areas of the
chromatin (Kalashnikova, 2016)
 Histone alterations are achieved through altering
chromatin accessibility or by integrating non-histone
effector protein
 which decodes the response encoded by the changing
arrays
 Inheritance process of this histone code yet to be explored

Literature Review :Epigenetic mechanisms
in Cancer…
Histone modifications…
 Histone alteration can result in suppression or initiation
 Dependent on the type of residues that are changed
and the nature of existing modifications (Zentner and
Henikoff, 2013
 E.g. H3K27 (H3K27me3) and H3K9 (H3K9me3) exists at
transcriptionally suppressed gene promoters
 Their alterations make up the two major silencing
process in mammalian cells
 Histone alternations: some determine cellular identity
(Ramos et al., 2013)).

Literature Review :Epigenetic mechanisms
in Cancer…
Histone modifications…
Epigenetic gene silencing mechanisms in mammals
Johnson et al. (2015)

Literature Review :Epigenetic mechanisms
in Cancer…
Nucleosome positioning
 Non-covalent process and have specific histone that determines
the manner in which chromatin makeup controls the activities of
the gene
 Nucleosomes control gene manifestation through modifying the
ease of access of governing DNA arrangements to transcription
elements (Struhl and Segal, 2013)
 NFRs exist at the fifth and third ends terminals of the genes
 offer the assembly and disassembly sites of the transcription
mechanism (Chen et al., 2013)