Chapter 37: Regulation Of Gene Expression Flashcards
What occurs at BOTH the DNA and histone level?
• Methylation‐ Both DNA and histones
• Acetylation‐ only histones
• Deacetylation – only histones
**What changes the activity of a DNA segment WITHOUT changing the DNA sequence? Does it typically activate or repress? Purpose?
- Methylation
- DNA methylation typically acts to REPRESS gene transcription
- Purpose (less HY): essential for normal dev (genomic imprinting, X‐chromosome inactivation, repression of transposable elements, Carcinogenesis)
In DNA methylation a methyl group is enzymatically added to _____________ via specific methyltransferases. _____ is usually the recognition sequence
- cytosines
- CG
What do methylated bases serve as binding sites for? Effect?
- methyl‐CpG‐binding domain proteins (MGDs)
- Effect: BLOCKS transcription(block transcription factor assembly, block chromatin remodeling, and also recruit histone deacetylases)
Methylation is CELL AND TISSUE SPECIFIC… when is this programmed?
- Early development, during cell differentiation
Example: Brain‐specific genes methylated in liver cells and vice versa
What is the total collection of structural DNA alterations that affect expression, but do not change the code?
Epigenetics: main components are DNA methylation (MOST IMPT) and histone modifications (phosphorylation, acetylation, ubiquitylation, etc)
**the alterations are passed through somatic cell lines during gamete formation to the offspring
Somatic cell nuclear transfer procedure? What is the Reproductive Animal Cloning Theory?
- Take nucleus out of donor somatic cells (some genes methylated)
- Inject into empty egg and implant into surrogate
**3. All methylated DNA gets demethylated (reset)
Theory is that offspring will have identical genome as donor
Issues with the Reproductive Animal Cloning Theory:
- Demethylation is never complete (few are still methylated) in the egg. So, the new animal has a few genes permanently “OFF” —> PREMATURE DEATH
**Most clones die young because of this
Altered DNA methylation has been linked to gene expression changes in:
cancer, embryo development and stem cell differentiation, drug and alcohol addiction, psychiatric disorders, healthy aging, and environmentally induced changes in twins
What is the process by which methyl groups are transferred to amino acids of histone proteins? Result?
- Histone methylation: condenses DNA backbone
- Typically acts to block transcription (can activate or block —> depends which AA is methylated)
**Histone Methylation process:
- Process: Histone methyltransferase transfers methyl groups from SAM (S-adenosyl methionine) to TWO SPECIFIC amino acids on the H3/H4 histones: LYSINE (K) and ARGININE (R)
What enzyme removes the methyl group on a histone?
histone demethylase
**Histone acetylation transfers an acetyl group to a _______ residue on a histone by the enzyme _________________. What is the result?
- lysine
- histone acetyltransferase (HAT)
- Result: The DNA is released from the histone for transcription
**Histone Deacetylation removes an acetyl group from the _______ residue on a histone by the enzyme __________. Result?
- lysine
- histone deacetylase (HDAC)
- Result: DNA packs tightly around histone
**What are proteins that bind to DNA and directly alter the recruitment, binding, and movement of basal transcription factors and RNA polymerase?
Gene regulatory transcription Factors
**can block/stabilize binding
**required to bind the promoter and recruit DNA pol for transcription
***What are DNA sequences that bind enzymes to promote or stop transcription?
Enhancers and Repressors
**Binding to an _________ bends DNA to ALLOW for transcription
enhancer
What is the loss of a methyl group in the 5-methylcytosine nucleotide? What is this associated with?
- hypomethylation
- Many cancers
*****What is the process by which only one copy of a gene in an individual (either from their mother or their
father) is expressed, while the other copy is suppressed?
•Imprinting: the gene is “stamped” according to paternal or maternal origin
**males and females DO NOT contribute same amts of genetic material to their offspring
Because of the concept of imprinting, ____________ genes are now assumed to have disproportionate effects on gene expression (long assumed to be equal)
- Autosomal genes: this is the concept that males and females are equally likely to inherit a gene
**What condition results from a child missing a small region on long arm of chromosome 15 and is this inherited from the FATHER? Signs/Symptoms?
- Prader-Willi Syndrome (Willi = penis = father): associated with imprinting
- Signs/Symptoms: small hands and feet, short stature, poor sexual development, intilectual disability, frequently obese
**Constant starvation feeling even though the child only needs 1/2 as many calories
**What condition results from a child missing a small region on long arm of chromosome 15 and is this inherited from the MOTHER? Signs/Symptoms?
- Angelman syndrome (Moms = angels): assoc with imprinting
- Signs/Symptoms: frequent laughter, uncontrolled muscle movement, large mouth, unusual seizures
**What condition results from a change on chromosomes 7 or 11 (MC)? Signs/Symptoms?
- Silver-Russell Syndrome
- Signs/Symptoms: intrauterine growth restriction and poor growth after birth, large head, prominent forehead, triangular face, body asymmetry, feeding difficulties
**What condition results from a change on chromosomes 11p15.5? Signs/Symptoms?
- Beckwith-Wiedemann Syndrome (B = BIG)
- Signs/Symptoms: overgrowth syndrome (macrosomia), enlarged tongue, abdominal abnormalities
**NORMAL life expectancy
How can Lifestyle and diet can affect epigenetics?
- Veggies/Egg yolk/soy: good methyl donor sources
Hypomethylation can cause cancer —> changes in diet /exercise can help - Wine: removes acetyl groups from histones
- Meditation and rest: increases telomerase activity