Epigenetics Flashcards
Epigenetic Trait
Stable, mitotically and meiotically heritable phenotype that results from changes in gene expression without alterations in the DNA sequence
Epigenetics
Study of the ways in which these changes alter cell- and tissue-specific patterns of gene expression
Epigenome
Refers to the Epigenetic state of a cell
Epigenetics have been implicated in:
- Progressive restriction of gene expression during development
- Allele-specific expression in gene imprinting
- Environment genome interactions during prenatal development that affect adult phenotypes
Abnormal regulation of the epigenome leads to human genetic disorders such as:
Prader-Willi syndrome, Angelman syndrome, and Beckwith-Weidemann syndrome
Epignetic changes occur through three major mechanisms:
Methylation: reversable; addition or removal of methyl groups
- Histone modification and chromatin remodeling: alter the accessibility of genes for transcription
- Non-coding RNA
Methylation
- DNA takes place after replication and during differentiation of adult cells
- Addition of a methyl group catalyzed by methyltransferase enzymes
- Occurs on cytosine bases adjacent to guanine called CpG dinucleotides
CpG Islands
Located near promoter sequences adjacent to genes
Histone Modification
- Chromatin is composed of DNA wound around an octamer of histone proteins to form nucleosomes
- Modifications occurs at conserved amino acid sequences in the N-terminal histone tails
- Chemical modification of histones alters the structure of chromatin, making genes accessible or inaccessible for transcription
Acetylation by Histone Acetyltransferase (HAT)
Opens up the chromatin structure, making genes available for transcription
Removal of the Acetyl groups by Histone Deacetylase (HDAC)
Closes the configuration, silencing genes by making them unavailable
Histone Code
Sum of the complex patterns and interaction of histone modifications that change chromatin organization and gene expression
RNA Interference
After transcription miRNA molecules associate with protein complexes to form RNA-induced silencing complexes (RISCs)
Long noncoding RNA (lncRNA)
- Share many properties with mRNAs (5’ caps, 3- poly-A tails, splicing)
- Found in nucleus and cytoplasm of cells
- lncRNAs lack frame that codes for the insertion of amino acids into a polypeptide
- Binds to chromatin-modifying enzymes
Imprinting
- Imprinted genes show expression of only the maternal allele or the paternal allele
- Parent-specific pattern of allele expression happens occurs during gamete formation
Once a gene has been methylated and imprinted:
- Remains transcriptionally silent during embryogenesis and development
- Most imprinted genes direct aspects of growth during prenatal development
Reprogramming
Occurs in the parental germ line and in the developing embryo just before implantation
Human disorders
Associated with imprinting have their origins during fetal growth and development
Cancer
- Hypomethylation is a property of all cancers examined to date
- Complex diseases have some strong links to environmental factors (lung cancer)
- Now viewed as a disease that involves both epigenetic and genetic changes that lead to alterations in gene expression
DNA Hypomethylation
Reverses the inactivation of genes, leading to unrestricted transcription of many gene sets including oncogenes
Hypermethylated genes
Include those involved in DNA repair, differentiation, apoposis, and drug resistance
Evidence that supports stem cell involvement in epigenetic changes
- Epigenetic changes can replace mutation in silencing individual tumour-suppressor genes or activating oncogenes
- Global hypomethylation may cause genome instability and the large-scale changes chracteristic of cancer
- Epigenetic modifications are more effective than mutations in transforming normal cells int malignant cells
Epigenetic Therapy
Reactivation of genes that have been silenced by methylation or histone modification
Environmental Agents
Nutrition, chemicals, and physical factors such as temperature can alter gene expression by affecting the epigenetic state of the genome
NIH Roadmap Epogenomics Project
Many aspects of health and susceptibility to diseases are related to epigenetic regulation or misregulation of gene activity
Human Epigenome Project
- Collects and catalogs data on a set of human epigenomes to serve as reference standards
- Multinational, public/private consortium established to identify , map and establish the functional significance of all DNA methylation patterns in the human genome
