Untitled
Epigenetics Overview
Definition of Epigenetics:
Study of heritable changes in gene expression that do not involve changes to the underlying DNA sequence.
Epimutation: Epigenetic inheritance or transgenerational epigenetic inheritance where epigenetic changes are passed from parent to offspring. However, not all epigenetic changes are inherited.
Learning Outcomes
Define epigenetics and epigenetic inheritance.
Outline types of molecular changes underlying epigenetic gene regulation.
Distinguish cis- and trans-epigenetic mechanisms that maintain changes.
Compare programmed epigenetic changes during development with those caused by environmental agents.
Explain differences between euchromatin and heterochromatin.
Describe functional roles of heterochromatin.
Distinguish between constitutive and facultative heterochromatin, and their similarities and differences.
Explain retaining heterochromatin patterns during cell division.
List molecular changes promoting heterochromatin formation, and their silencing effects on genes.
Describe examples of human diseases caused by heterochromatin abnormalities.
Describe genomic imprinting mechanism of the Igf2 gene in mammals.
Outline the process of X-chromosome inactivation.
Describe pioneer factors' functions.
Explain epigenetic modifications' involvement in developmental changes leading to specific cell types.
Define paramutation.
Explain persistence of paramutations across generations.
Describe epigenetic changes underlying paramutations.
Explain coat color modification in mice via dietary factors.
Describe evidence of queen honeybee development due to royal jelly exposure.
Explain temperature-controlled flowering in certain plant species.
Types of Epigenetic Modifications
DNA Methylation:
Methyl groups attached to cytosine bases in DNA;
Inhibition of transcription when methylation occurs near promoters.
Chromatin Remodeling:
Nucleosomes can be repositioned or evicted affecting transcription levels;
Significant structural changes occur, e.g., during X-chromosome inactivation in females.
Covalent Histone Modifications:
Amino acid side chains in histone tails can be modified (e.g., acetylation, phosphorylation);
These modifications can enhance or inhibit transcription.
Localization of Histone Variants:
Histone variants can be localized near gene promoters affecting transcription.
Feedforward Loop:
Activation of a transcription factor that stimulates its own expression through a positive feedback mechanism; more common in microorganisms.
Epigenetic Changes: Cis vs. Trans
Cis-epigenetic changes:
Maintained at specific local sites; e.g., modifications affecting nearby genes.
Trans-epigenetic changes:
Affect distant genes, often through transcription factors regulating multiple gene expressions.
Developmental Epigenetic Changes
Programmed Changes During Development:
Genomic Imprinting: Differential DNA methylation in genes like Igf2 during oogenesis and spermatogenesis affects allele expression in offspring.
X-chromosome Inactivation: XCI during embryogenesis in females is an essential epigenetic change for dosage compensation.
Cell Differentiation: Involves epigenetic changes like DNA methylation and histone modifications that dictate the specific cell types.
Environmental Agents Influencing Epigenetics
Temperature Effects:
Cold temperatures in plants can lead to histone modifications that prepare for spring flowering and germination.
Diet:
Varied diets of honeybees affect DNA methylation patterns, influencing gene expression between queens and workers.
Toxins:
Cigarette smoke and heavy metals (cadmium, nickel) can alter DNA methylation and histones, potentially leading to diseases like lung cancer.
Heterochromatin: Function and Characteristics
Euchromatin vs. Heterochromatin:
Euchromatin: Less compact, transcriptionally active.
Heterochromatin: Densely packed, primarily transcriptionally inactive regions found at the nuclear periphery, attached to the nuclear lamina.
Functional Roles of Heterochromatin:
Gene silencing to prevent the movement of transposable elements and control viral proliferation.
Constitutive Heterochromatin:
Always present in the same location across cell types, includes repetitive sequences, characterized by DNA methylation and specific histone modifications (e.g., H3K9me3).
Facultative Heterochromatin:
Reversible formation; can silence genes during specific developmental stages, usually modified by environmental factors.
Higher Order Structure of Heterochromatin
Molecular Events:
Assembly of nucleosomes into stable 3D structures through interactions and phase separation.
Formation of loop domains and stable nucleosome contacts via proteins like HP1 and SMCs.
Liquid-Liquid Phase Separation (LLPS):
Heterochromatin can form liquid-like droplets contributing to gene regulation and chromatin organization.
Maintenance of Heterochromatin
Transmission to Daughter Cells:
Pattern and structure of heterochromatin are retained during cell division through DNA methylation, histone modifications, and interactions with chromatin remodeling complexes.
Embryonic Development:
Epigenetic changes occurring early in development ensure daughter cells develop into specific cell types by maintaining gene activity patterns.
Roles of Pioneer Factors in Epigenetics
Definition:
Transcription factors capable of altering chromatin structure; they bind to regulatory regions prior to transcriptional activation.
Mechanisms:
Recruit chromatin remodelers and histone modifiers, decreasing DNA methylation, and helping to establish transcriptional networks during differentiation.
Importance:
Comprise key components in driving developmental changes, yielding potential for certain genes while repressing others.
Functional Outcomes:
Affect the transcription landscape, variations in gene expression rates during embryogenesis, and among differentiated cell types.