Epigenetic Regulation Flashcards
What kind of transcription control is generally seen in eukaryotes?
Combinatorial control: Different regultory proteins can bind to the same regulatory sequence in DNA. The combination of regulatory proteins that bind to a regulatory element depends on the type of cell or the physiological state of the cell. Specific combinations of regultory proteins express or repress transcription.
Describe the structure of Myc, Max, and Mad
Family of bHLH-ZIP transcription factors that can acts as homodimers or heterodimers. Have a helix-loop-helix structure and interact noncovalently through their leucine zippers. Max is constituitively expressed.
Mad and Myc have have opposing functions in transcription and Max plays a central role
When is Myc only expressed
G1 to S transition of the cell cycle
Max-Max
ebox gene not transcribed
Myc-Max
Cell proliferation. Synthesis of genes required for entering into S phase
Mad-Max
Inhibit proliferation and initiate differentiation
Ebox
Gene elements required for cell division
Max-Max : silences
Myc-Max : Expression
Mad-Max : Repression
Describe the ways in which the activity of gene regulatory proteins is regulated in eukaryotic cells
1) The protein is synthesized only when needed and is rapidly degraded by proteolysis so that it does not accumulate
2) Activation by ligand binding
3) Activation by phosphorylation
4) Formation of a complex between a DNA-binding protein and a seperate protein with a transcription activating domain ( addition of a second subunit)
5) unmasking of an activation domain by phosphylation of an inhibitor protein
6) Stimulatoin of nuclear entry by removal of an inhibitory protein that otherwise prevents entry
7) Releasing a regulatory protein from a membrane bilayer by regulated proteolysis.
***each of these mechanisms is typically controlled by extracellular signal which are communicated across the plasma membrane to the gene regulatory proteins in a cell*
Describe how different signal transduction pathways activate kinases that regulate the AP-1 transcription factors Jun and Fos
ERK phophorylates Fos and JNK phosphorylates Jun. Jun and Fos then dimerize to form AP-1 and along with Ets. These activate transcription of genes that control proliferation and anti-apoptotic signals
Jun and Fos are bZIP proteins that heterodimerize through leucine zippers and bind with the scissor motif to the AP-1 element in the gene regulatory region.
Describe ways in which chromatin structure regulates gene expression
- positioning a gene in condensed or heterchromatin inhibits gene expression
- Histone acetylation opens chromatin and de-acetylation condenses chromatin
- histone methyltion regultes chromstin structure in a manner that depends on the histone residue modified. generally de-methylation regulates the chromatin in a way opposite of the signal that the original methylation sends. so if methylation reduces transcription than de-methylation will increase trancription and vice-versa
Why does X-inactivation occur in females?
Because if there was no X inactivation then the dosage of X gene products in females would be twice that of males and would be toxic to the female.
How does X inactivation occur in females
During embryogenesis the placenta sends a signal to the embryo cells. This causes non coding RNA to coat the maternal X chromosome in some cells and the paternal X in others. Next the X chromosome marked or inactivation undergoes de-acetylation and methylation by which it is silenced. This epigenetic modification is inherited by future somatic cells and females are a mosaic of cells that contain either an actice maternal or active paternal X
Explain the role of the locus control region (LCR) in regulating ß-globin gene expression in red blood cells
The ß-globin gene is part of a cluster of globin genes. The LCR is located upstream of this cluster and is shared by all the globin genes. Each globin gene has it’s own set of regultory sequences, but the LCR is like the master “on” switch. Gene regulatory proteins bind to the LCR and through DNA looping interact with proteins bound to the the individual gene control regions for each globin gene. The importance of the LCR is seen in patients with a certain thalassemia where all or part of the LCR sequence is deleted. Even though the ß-globin gene has it’s own regulatory sequences it will remain transcriptionally silent when the LCR is deleted.
Why is the LCR important?
The importance of the LCR is seen in patients with a certain thalassemia where all or part of the LCR sequence is deleted. Even though the ß-globin gene has it’s own regulatory sequences it will remain transcriptionally silent when the LCR is deleted. patents with this deletion suffer from severe anemia. The LCR also contains a barrier sequence that prevents heterochromatin from spreading to the ß-globin gene.
What does epigenetic mean?
Epigenetic refers to the inheritance or passage of information from parental cells to progeny cells through a mechanism other than the “instructions” present in the nucleic acid sequence of the copied DNA.
Two alleles can have the same genetic sequence but different inheritable genetic information
Epigenetic mechanisms occur through either modification of DNA or regulatory proteins
What is the importance of combinatorial gene control in development?
When an embryonic cell divides one of its daughters makes a regulatory protein and the other does not. The daughter cells of the embryo sense the presence or abscence of these regulatory proteins which cause them to produce a unique combination of regulatory proteins within themselves. These combinations are inherited down the cell line and eventually lead to tissue differentiation based on the unique combination of regulatory proteins the cells in those tissues posess.
