Week 7 Flashcards
Is there a relationship between organism complexity and gene number?
There is a non-correlational relationship
What is epigenetics?
The study of how your behaviors and environment can cause changes that affect the way your genes work
Is there a Nobel Prize for genetics?
Svante Pääbo won the 2022 Nobel Prize in physiology or medicine for his pioneering work in deciphering the genetics of our hominid relatives, Neandertals and Denisovans
What is the Waddington landscape?
A visual metaphor for the development of multicellular organisms
What does the regulation of gene expression involve?
A wide range of mechanisms that are used by cells to increase or decrease the production of specific gene products
What is chromatin?
A mixture of DNA and proteins that form the chromosomes found in the cells of humans and other higher organisms
What is the epigenetic code?
It describes the way in which the potential for expression of genes in a particular cell type is specified by chromatin modifications put in place at an earlier stage of differentiation
How does chromatin relate to epigenetics?
Epigenetic processes control gene expression by altering chromatin structure
What is the hypoxia-inducible factor?
A heterodimeric transcription factor governing a transcriptional program in response to reduced O2 availability in metazoans
What does HIF contribute to?
Physiology and pathogenesis of many human diseases through its downstream target genes
At what level does epigenetics occur?
Epigenetic processes, including DNA methylation, histone modification and various RNA-mediated processes, are thought to influence gene expression chiefly at the level of transcription; however, other steps in the process (for example, translation) may also be regulated epigenetically
What is Hi-C?
A genome-wide chromatin conformation capture protocol that uses proximity ligation
What does DNA methylation play a pivitol role in?
Many biological procedures such as gene expression, embryonic development, cellular proliferation, differentiation and chromosome stability
What is aberrant DNA methylation associated with?
Loss of DNA homeostasis and genomic instability leading to development of human diseases such as cancer
What does the importance of DNA methylation create?
An urgent demand for effective methods with highly sensitivity and reliability to explore innovative diagnostic and therapeutic strategies
What as bisulfite genetic sequencing recognised as?
A revolution in DNA methylation analysis based on conversion of genomic DNA by using sodium bisulfite
What is ATAC-Seq?
The assay for transposase-accessible chromatin with sequencing (ATAC-Seq) is a popular method for determining chromatin accessibility across the genome
What is the function of ChIP-Seq?
Identifies the binding sites of DNA-associated proteins and can be used to map global binding sites for a given protein
What is the advantage of single cell technology?
Compared with traditional sequencing technology, single-cell technologies have the advantages of detecting heterogeneity among individual cells, distinguishing a small number of cells, and delineating cell maps
Which transcription factors are involved in epigenetics?
Histone modifications, DNA methylation and RNA-mediated silencing are well defined, DNA-independent epigenetic mechanisms that regulate gene expression
Where does the epigenetic landscape play a crucial role in?
Cellular adaptation, as it integrates the information generated from stimuli
What are signalling pathways induced?
By stimuli communicate with chromatin to change the epigenetic landscape through regulation of epigenetic modifiers
What do altered metabolic dynamics effect?
The activity of epigenetic modifiers
What can epigenetic reprogramming increase?
The susceptibility to many diseases in adulthood
Where is the programming of the epigenome occur?
Via the activity of a variety of epigenetic modifiers, including “readers, writers and erasers” of histone methyl marks
What does a histone acetylation do?
Histone acetylation is a critical epigenetic modification that changes chromatin architecture and regulates gene expression by opening or closing the chromatin structure
What is histone methylation?
The modification of certain amino acids in a histone protein by the addition of one, two, or three methyl groups
What is DNA methylation at promoters largely correlated with?
Inhibition of gene expression
How are eukaryotic genomes partitioned?
Into euchromatic and heterochromatic domains to regulate gene expression and other fundamental cellular processes
What do siRNAs promote?
Heterochromatin formation, but little is known about how chromatin regulates siRNA expression
What do stem and progenitor cells have the capacity for?
Balancing self-renewal and differentiation
What is the function of hematopoietic myeloid progenitors?
They replenish more than 25 billion terminally differentiated neutrophils every day under homeostatic conditions and can increase this output in response to stress or infection
What are the key players in cancer development?
Epigenetic mechanisms
What can result from alterations in chromatin and DNA methylation?
Genetic lesions unleash cellular plasticity and favor oncogenic cellular reprogramming
How is epigenetics a cellular clock?
They can mark accurate chronological time versus biological time. Our chronological age is based on our birthdate, but biological age means the true age that our cells, tissues, and organ systems appear to be, based on biochemistry
What is the relationship between aging and epigenetics?
The regulatory epigenetic machinery becomes gradually deregulated leading to an altered epigenetic state during aging, a process we call epigenetic drift
What is the link between epigenetics and cancer?
Disruption of epigenetic processes can lead to altered gene function and malignant cellular transformation
What is the biggest paradox of cellular differentiation?
How cells with identical DNA sequences differentiate into so many different cell types
What mediates epigenetic regulation?
Alterations in DNA methylation, histone posttranslational modifications, and nucleosome remodeling
How is the epigenome altered?
Lifestyle and environmental factors (such as smoking, diet and infectious disease) can expose a person to pressures that prompt chemical responses
What genes are mutated most frequently during cancer?
The most commonly mutated gene in people with cancer is p53 or TP53
What are synovial sarcomas?
A type of Soft Tissue Sarcoma (STS) and represent 8–10% of all STS cases
What is diffuse intrinsic pontine glioma?
A lethal pediatric tumor with no currently available treatment options
What is the percentage of DIPG mutations that carry the K27M mutation specificlly?
60-70%
What is acute myeloid leukaemia?
A heterogeneous hematologic malignancy in terms of clinical features, underlying pathogenesis and treatment outcomes
What has the recent advances in genomic techniques unraveled?
The molecular complexity of AML leukemogenesis, which in turn have led to refinement of risk stratification and personalized therapeutic strategies for patients with AML
What do the majority of leukaemia’s result from?
MLL1 fusions with one of about six common partner genes
What percentage of leukemias harbour MLL1 translocations?
10%
What does most molecular medicine still lack?
The ability to elucidate hidden mechanisms for the maintenance of specific subclasses of rare tumors characterized by the silent onset and a poor prognosis
What is BRD4?
A member of the Bromodomain and Extraterminal (BET) protein family & acknowledged in cancer for its role in super-enhancers (SEs) organization and oncogenes expression regulation
What does the inhibition of BRD4 shortcut?
The communication between SEs and target promoters with a subsequent cell-specific repression of oncogenes to which cancer cells are addicted and cell death
What are BET inhibitors?
A class of small molecules targeting BET proteins which are currently in clinical trials in several cancer settings
What do epigenetic therapies seek to do?
Normalize DNA methylation patterns and post-translational modifications on histones that promote or maintain a malignant phenotype
What is the success rate of immunotherapy for cancer?
Overall response rates are about 15 to 20%
What is a beneficial cancer therapy utilising BET domains?
Restoration of anti-tumor immunity by blocking PD-L1 signaling using antibodies
What are both MHC class I antigen presentation pathway (MHC-I APP) mutations and transcriptional repression of MHC-I associated with?
Resistance to immune checkpoint inhibitors
Is plasticity an adaptation?
Organisms respond to different environments by changing how they act, look or function. When these responses improve the chances of survival, we call them adaptive plasticity
What are 3 factors that affect epigenetics?
Several lifestyle factors have been identified that might modify epigenetic patterns, such as diet, obesity, physical activity, tobacco smoking, alcohol consumption, environmental pollutants, psychological stress, and working on night shifts
What is DNA cloning?
A molecular biology technique that makes many identical copies of a piece of DNA, such as a gene
What does a typical cloning experiment involve?
A target gene is inserted into a circular piece of DNA called a plasmid
What process allows a plasmid to be introduced into bacteria?
Transformation
What is non-genetic transcriptional variability?
A potential mechanism for therapy resistance in melanoma. Specifically, rare subpopulations of cells occupy a transient pre-resistant state characterized by coordinated high expression of several genes and survive therapy
