Epigenetics and Cancer Flashcards
What are epigenetics?
- mechanisms that regulate gene expression
- ex. methylation, histones and histone acetylation, histone variants that alter chromatin structure, mRNA degradation induced by microRNAs
Proteins involved in epigenetic DNA regulation
- DNA methyltransferases
- Histone modifiers
- Chromatin remodelers
How do methyltransferases function?
- methyl groups on CpG islands inhibit gene transcription
- also increase binding of transcriptional repressors
Is the DNA in our nucleus organized in linear strands?
- no
- wrapped around proteins (histones)
- histones form fibres called chromatin
- chromatin unwinds when necessary so transcription or replication is necessary
Which enzymes are considered the “writers” and “erasers” for histone modification?
Writers
- histone acetyltransferases
- histone methyltransferases
Erasers
- histone deacetylase
- histone demethylase
What do epigenetics have to do with cancer?
- cancerous cells are found to have global irregular epigenetic landscapes
- very common for cancerous cells to have many mutations in genes coding for epigenetic regulators
What type of cancer are we focusing on learning?
- cutaneous squamous cell carcinoma (cSCC)
3 types of cells in the epidermis
keratinocytes - epithelial cells
melanocytes - synthesize melanin
langerhans cells - immune protection
Functions of epidermis
- prevents water loss
- protection against chemicals, pathogens, UV radiation, and physical insults
- temperature regulation
- electrolyte balance
What is basal cell carcinoma?
- most common form of skin cancer
- transformation of the basal keratinocytes
Etiology - chronic UV exposure, ionizing radiation
What is melanoma?
- 4% of all cancers in canada
- very aggressive and highly metastatic
- transformation of melanocytes
Etiology - chronic UV exposure, familial mutations
What is cutaneous squamous cell carcinoma?
- accounts for 20% of all skin cancers in canada
- second most cancer in humans
- transformation of epidermal stem cell keratinocytes in basal layer of skin or hair follicles
Risk factors - UV radiation, immunosuppression
Organization of epidermis cells from superficial to deepest
- Corneocytes
- Granular keratinocytes
- Spinous keratinocytes
- Basal layer (stem cells and transit amplifying cells)