HMB265H1 Lecture Notes - Lecture 19: X-Inactivation, Xist (Gene), Dosage Compensation

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23 Mar 2016

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Epigenetic changes cause coat colour differences in mice these changes can be influenced by the environment. All the mice are heterozygotes at the agouti locus: there is a mutation in the agouti gene (a) - null, results in iap element (inhibitor of apoptosis) Mother"s diet during pregnancy can cause epigenetic changes in offspring. Epigenetic regulation means different coat colours in genetically identical mice alleles identical. X-chromosome inactivation: random x-chromosome inactivation in females early during development, silencing of the chromosome only happens in x-chromosome, this happens in every cell in the female body. This happens early in development all of the future clonal descendants will have the same pattern: leads to a mosaic type of colour. Although x-inactivation is maintained over 1000s of cells it is not always permanent. Mechanism of x-inactivation i. e. germ line cells will reactivate them before dividing. Hypoacetylation of lys in two histone, methylation of inactivated x what xist does.

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1) In the wildtype (the DNA sequence most commonly found in nature) lac operon, transcription is severely down-regulated. A mutation in lacI that causes an early stop codon in the sequence (called a lacI - strain) results in an operon that has high levels of transcription of the polycistronic m-RNA. What type of regulatory protein is the LacI protein (hint: we covered this type of protein in lecture)?

The Lac regulatory protein is called a repressor. (is this correct)

2) If a bacterium with a wildtype lac operon is grown in the presence of lactose, high levels of transcription result for a while, however, eventually transcription is again down-regulated. If, on the other hand, the sugar IPTG is present (instead of lactose), transcription levels are high and remain high. What function do IPTG and lactose share? How are they differently affected by the operon product? (need help with this question)

Lactose and IPTG affected by the operon are both inducers of the Lac-Operon. (is this correct)

3) What is âepigeneticsâ? What forms of gene regulation are usually involved in epigenetic control of a trait? Why do we have such a limited understanding of epigenetic processes? (need help with this question)

Epigenetics is the study of phenotype changes that do not change the DNA sequence. Genes can be turned on and off based on environment situations of past generations, (parents or even grandparents) were exposed. Examples of some environmental factors could be diet, stress, smoking, drinking alcohol, and diseases. Histone modification and methylation are usually involved in epigenetic control of a trait. (is this correct)

Part III â Just How âIdenticalâ Are We?

Elise had been home from college for a week, and she was still preoccupied with Shannonâs diagnosis and her own potential risk for mental illness. Elise expressed her anxiety and concerns to her mother one night after dinner. âElise,â her mother said, âyour concerns are perfectly valid, and you have every reason to want to get more information. Why donât we make you an appointment to consult with a psychiatrist?â Elise decided to make the appointment the next day. * * * * * Elise left Dr. OâBrienâs offi ce feeling that some of the weight had been lifted from her shoulders. On the car ride home, she thought about the things that Dr. OâBrien had said to her during their consultation. âIt was good of you to come in to see me, Elise. You are absolutely right to have concerns for yourself when your identical twin has been diagnosed with schizophrenia. Research shows that schizophrenia is almost 50% heritable, and since you share nearly identical DNA with your sister, that puts you at a higher risk for developing this disease as well.â âFifty percent may sound like a scary number, but remember that schizophrenia is a very complex disease, and 50% of what causes schizophrenia is due to things other than your DNA.â âWell, like what? What else could be contributing to Shannonâs schizophrenia that wouldnât necessarily aff ect me?â Elise asked. Dr. OâBrien replied, âTh ere are many, many environmental infl uences that seem to play a role in the development of this disease, such as increased stresses and anxiety, or diffi cult relationships with other people. Interestingly, there is some groundbreaking research that is going on that suggests that the environment itself might even play a role at infl uencing oneâs DNA at the molecular level. Th is concept is called epigenetics. An example of epigenetics in nature is the calico cat. Each calico cat has a unique orange and black fur color pattern because of alterations, called epigenetic changes, which occur within the cells that produce coat color during the catâs development. Research in the fi eld of epigenetics suggests that individuals with schizophrenia appear to have some of these epigenetic changes to their DNA that are due to environmental infl uences, and that these alterations could be contributing to their development of mental illness.â âBut wouldnât I also have these âepigenetic alterationsâ in my DNA?â Elise asked. âNot necessarily, because you and Shannon have not experienced completely identical environments throughout your lives. For example, you and Shannon have had diff erent teachers and jobs throughout high school. And I also understand that you spent many childhood summers with a friend and her family out in the Grand Canyon, while your sister was off at swim camps. If you are interested, I can give you some literature to read about this subject.â Elise was defi nitely interested. She took the articles and headed home.

1. Briefly describe what you know about the structure of DNA and how DNA is packaged in a cell.

2. At the molecular level, speculate on some ways that the environment might have an infl uence on DNA and its packaging

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HMB265H1 Lecture Notes - Lecture 19: X-Inactivation, Xist (Gene), Dosage Compensation

HMB265H1 Full Course Notes

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