Theme 3 Applied Lecture 2 - Biology 1A - Fall 2024 Lecture Notes - PDF
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McMaster University
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This document is lecture notes from McMaster University, covering the principles of epigenetics and gene expression. The lecture focuses on how external factors can influence gene expression.
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Theme3AppliedLecture2-BIO1A03Fall2024 Wednesday, October 23, 2024 12:26 PM Theme3App liedLectur… Cells receive signals from environm - Domino effect! Leads to a re - Cells must interact with the ○ Happens through rece - Signal transduction ○ Passing on the signal/ - S...
Theme3AppliedLecture2-BIO1A03Fall2024 Wednesday, October 23, 2024 12:26 PM Theme3App liedLectur… Cells receive signals from environm - Domino effect! Leads to a re - Cells must interact with the ○ Happens through rece - Signal transduction ○ Passing on the signal/ - Short term ○ Modify immediate cel - Long term ○ Modification of gene e Are the genes that we want to exp Influenced by histone modification ment = changes in gene expression esponse signal eptors (either on the membrane or inside the cell) /transducing the signal/transmitting to different proteins in the cell ll processes, like post-translational modifications expression/development, like transcriptional (slowest) regulation press available to RNA polymerase? Or not? n, how accessible genes are to be expressed Are the genes that we want to exp Influenced by histone modification Epigenome = we all have, modfiic Means above the genome Controlling whether the genes ar - Epigenetic mechanisms ○ Histone tail modificat ○ DNA methylation (ho Overall result: Chromatin Remod press available to RNA polymerase? Or not? n, how accessible genes are to be expressed cations on the genome we get from our parents re on/off through chemical modifcations tions (is the gene unwound?) ow much DNA methylation there is, can transcription happen? delling Overall result: Chromatin Remod Ideal scenario: express our genes t Epigenetic mechanisms important - Everything we're exposed to ○ Aging ○ Diet ○ Environmental chemic ○ Development (in utero § What our mothe - Most cases cancer is not due ○ Have some promoters expressed as a result ○ Or less methylation tha delling throughout our lives ALL through life o in our environment can influence acetylation/methylation of DNA cals o) ers consumed affected our genome e to just mutations that are much more methylated in cancer cells than normal cells, less an normal cells, more expressed as a result - Epigenome of these cells, ch - When comparing breast can methylation (transcripted m - Uncontrolled growth - Formation of tumours - Higher levels of methylatio hemical modificatoins ncer cells to non cancerous breast cancer cells, there is less much more often) on on genes they want to turn off - Higher levels of methylatio ○ Ex. Gene that causes - Not just cancer mutations - A lot of it due to epigenetic on on genes they want to turn off s malfunctioning cells to self destruct (apoptosis) that are leading to changes in gene expression c mechanisms - Epigenetics is a mechanism w - Agouti mice (2003 study) ○ Difference between th § Size § Colour § Predesposition t disorders than th ○ But both mice are gene - Colour gene ○ When agouti yellow ge ○ In brown mice, gene is ○ In a network, contribut ○ Colours lets us pre-em we are exposed to through utero hem to disease (yellow mice more prone to cancer, diabetes, metabolic he brown mice) etically identical enes expressed, you get yellow colour instead of traditional brown s kept on te to cancer, diabetes, metabolic disorders mptively suspect the prone to sickness in the yellow mice ○ ○ In brown mice, gene is ○ In a network, contribut ○ Colours lets us pre-em Agouti gene = yellow colour When not methylated, the mice a When methylated, thin, brown, he s kept on te to cancer, diabetes, metabolic disorders mptively suspect the prone to sickness in the yellow mice are yellow, obese, prone to cancer & diabetes ealthy Why was this so important? - First group of people who - They showed that through outcome of offspring in a l individual's lfie - In the beginning, a lot of y ○ Prediction: if we give are yellow, predispo ○ Mice that are produ ○ Predicted that meth possibly control how sugar levels looked into epigenetic regulation of gene expression h methylation, epigenetic mechanisms, you could change the possible litter, and continue modifying an epigenome throughout the yellow obese mice e no methyl supplement in the diet, most mice willl be yellow (parents osed to having cancer diabetes etc) uced will mostly be yellow, same predisposition hylation was controlling whether the mcie were yellow, and could also w much these mice develop cancer tumours diabetes and their blood - Had another group of mice, lo ○ Prediction: offspring mo ○ Reality: most of them w active - Did this for various sources of ○ More methyl = more bro oaded their diet with methylated supplements ostly yellow were brown! No tumourous masses, no diabetes, healtheri outlook, more f methyl own Still identical genes! But epigenet survival than yellow mice tic mechanisms are altered, giving brown mice a higher chance of Unsupplemented: - Mostly yellow Supplemented: - Mostly brown Identical twins - Monozygotic (came from th - Random splitting that leads - Same parents, same single f he same fertilized egg) to two separate embryos fertilized egg - Clump of cells (dividing con - Then clump of cells collaps - Clump of cells (dividing con - Then clump of cells collaps - Outer casing collapses (bla - Becomes 2 clumps of cells - 2 clumps of cells all derive and twin 2 - Happens to all identical tw - While in utero, they will be medications and environm Exposed to the exact same things identicaL twins look exact same w ntinuously) se astociss) from same embryonic stem cells same fertilized egg and become twin 1 wins e exposed to same methyl/acetyl groups the mom consumes, same ment when they're young - Identical twins develop diffe ○ Diverge in appearance ○ Rooted in epigenetic m erent lifestyles e over time due to diverging lifestyles over time mechanisms, since genes and DNA are the same