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Questions and Answers
What is the primary result of hypermethylation in tumor suppressor genes?
What is the primary result of hypermethylation in tumor suppressor genes?
Which type of DNA methylation is associated with global genomic implications in cancer development?
Which type of DNA methylation is associated with global genomic implications in cancer development?
In organic chemistry, what defines a methyl group?
In organic chemistry, what defines a methyl group?
What is the effect of acetylation on proteins?
What is the effect of acetylation on proteins?
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Which of the following statements about acetylation in bacteria is true?
Which of the following statements about acetylation in bacteria is true?
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What effect does plentiful food have on diabetes mortality in grandchildren?
What effect does plentiful food have on diabetes mortality in grandchildren?
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Which chemical change occurs at CpG sites during DNA methylation?
Which chemical change occurs at CpG sites during DNA methylation?
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What is the primary role of DNA methylation in gene expression?
What is the primary role of DNA methylation in gene expression?
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Which regions of the human genome are typically not methylated?
Which regions of the human genome are typically not methylated?
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What is the general fidelity of DNA methylation patterns in somatic cells during cell division?
What is the general fidelity of DNA methylation patterns in somatic cells during cell division?
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Study Notes
Transgenerational Epigenetic Inheritance
- Increased diabetes mortality observed in grandchildren when food was plentiful, indicating epigenetic inheritance.
- Paternal granddaughters of women who experienced famine in utero had shorter average lifespans.
DNA Methylation in Cancer
- DNA methylation occurs primarily at CpG sites, converting cytosine to 5-methylcytosine via DNA methyltransferase.
- Around 80-90% of human CpG sites are methylated; CpG islands (65% CG residues) are typically unmethylated and associated with 56% of mammalian gene promoters.
- Aberrant DNA methylation leads to unscheduled gene silencing and is linked to cancer, manifesting as hypermethylation (gene repression) and hypomethylation (cancer progression).
Acetylation and Gene Expression
- Acetyl is a functional group with the formula COCH3; methyl is an alkyl group from methane (CH3).
- Acetylation significantly influences gene expression and metabolism, particularly in histones and metabolic enzymes.
- Overexpression of histone deacetylases (HDACs) is associated with tumorigenesis and metastasis, impacting oncogene expression.
Histone and Chromosomal Structure
- Human genome contains over 20,000 genes organized into 23 pairs of chromosomes, with DNA tightly wound around histones into nucleosomes.
- Nucleosomes can move to expose DNA for transcription through histone modifications (tags) signaling whether a region should be open or closed.
- Chemical modifications like phosphorylation, methylation, and acetylation affect histone charge and DNA winding.
Epigenetic Regulation
- Changes in histone proteins and DNA impact gene expression without altering the DNA sequence, classifying them as epigenetic modifications.
- The epigenetic regulation process allows for temporary changes that can persist through cell divisions, influencing transcriptional activity based on need.
Estrogen Receptor in Breast Cancer
- Estrogen receptor alpha (ESR1α) serves as a critical prognostic marker in breast cancer; about two-thirds of cases are ESR1-positive.
- Estrogen binding to ESR1 regulates mammary gland growth and differentiation, playing a role in breast cancer progression.
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