Control of Gene Expression Flashcards Preview

Biomedical Sciences Core > Control of Gene Expression > Flashcards

Flashcards in Control of Gene Expression Deck (21):
1

Importance of controlling Gene Expression


•All cells contain an identical set/s of genes.

•Only a small subset of these genes ________in a given ____ at a ____
–Cells adapt to changes of the ___ ____by controlling gene expression. (Avoid ___ Of ____)
–Alter expression of genes ____ ____ and also ___ ____

 


•All cells contain an identical set/s of genes.•Only a small subset of these genes will expressed in a given cell type at a given time.
–Cells adapt to changes of the external environment by controlling gene expression. (Avoid wastage of energy)
–Alter expression of genes during development and also cell differentiation.

 

2

Regulation of Eukaryotic Gene Expression at Multiple Levels

____/____ _____

____ of ___

___ ___ ____

___ of ___


•DNA/Chromosome remodeling

•Regulation of transcription

•Post transcriptional modifications

•Regulation of translation

 

3

Gene Expression Requires Chromatin Changes

 

  • •Heterochromatin
    •  
    •  
  • •Euchromatin
    •  
    •  
  • •Normally chromatin blocks _____ and ____  from ___ with DNA
     


•Heterochromatin
•Condensed throughout cell cycle
•Little or no gene expression
•Euchromatin
•Open, extended conformation
•Transcriptionally active
•Normally chromatin blocks transcription factors and Pol II from associating with DNA
 

4

Chromatin Remodeling 


•Displacement of____ from_____ DNA sequences to ___ ____. 
•Chromatin remodeling complex uses___ to ___ ____ stretches from the ___ ___.

•Covalent modifications of ____ through ____. (attachment of acetyl group to the ____ residue)
•Loss of ____ ____between the____ histones and the ____ charged DNA.
____ DNA from the histones.
 


•Displacement of nucleosome from specific DNA sequences to initiate transcription.
•Chromatin remodeling complex uses ATP to unwind DNA stretches from the nucleosome core.
•Covalent modifications of histones through acetylation. (attachment of acetyl group to the lysine residue)
•Loss of electrostatic interactions between the basic histones and the negatively charged DNA.
•Unwinds DNA from the histones.
 

5

Gene Specific Regulators (Repressors)


•Some gene specific regulators can ___transcription. (____)
•Binding of repressors to specific DNA sequences ___ an ____from binding to the DNA thereby ____ transcription.
•Repressors can bind to _____ which in turn prevent binding of co-activators. 
•Repressors can bind directly to components of the ___ ___ turning off transcription. 
 


•Some gene specific regulators can repress transcription. (repressors)
•Binding of repressors to specific DNA sequences prevents an activator from binding to the DNA thereby inhibiting transcription.
•Repressors can bind to co-repressors which in turn prevent binding of co-activators. 
•Repressors can bind directly to components of the basal complex turning off transcription. 
 

6

Methylation of DNA


•Nitrogenous base ____ in DNA can be____ to form ________
•Methylated cytosines are found in stretches of ____ rich regions of the DNA located near _____ regions.
•These regions ____ ___ _____  in the presence of methylated cytosines.

 


•Nitrogenous base cytosine in DNA can be methylated to form 5-methylcytosine.
•Methylated cytosines are found in stretches of GC rich regions of the DNA located near promoter regions.
•These regions can not be transcribed  in the presence of methylated cytosines.

 

7

Regulation of Transcription
 


•Transcription is controlled by the assembly and binding of the___ ___ ____ to distinct promoter elements.
•Complex consists of transcription factors _____, ____ and _______
•Additional transcription factors can bind ___ ____ within the promoter region.
•Genes that are exclusively regulated by the cis-acting elements within the promoter are ___ ____
 


•Transcription is controlled by the assembly and binding of the basal transcription complex to distinct promoter elements.
•Complex consists of transcription factors TFIID, TFIIA and RNA polymerase II.
•Additional transcription factors can bind upstream sites within the promoter region.
•Genes that are exclusively regulated by the cis-acting elements within the promoter are constitutively expressed. 
 

8

DNA Regulatory Sequences and Gene Specific Regulators (Activators)


•Some DNA regulatory sequences that are ____ to a gene/genes can ___ transcription (known as ___)
•Mainly located  a distance away___ or ___to the transcription site.
•The proteins that bind to these regulatory sequences are known as ___ ___ ___ ___ (____)
•They interact with the basal transcription complex via ___ ___ (___ ___) by ____-____interactions.
•This interaction will cause the ____ to ___ or ___
 


•Some DNA regulatory sequences that are specific to a gene/genes can increase transcription (known as Enhancers)
•Mainly located  a distance away upstream or downstream to the transcription site.
•The proteins that bind to these regulatory sequences are known as Gene specific transcription factors (activators)
•They interact with the basal transcription complex via mediator proteins (co-activators) by protein-protein interactions.
•This interaction will cause the DNA to loop and bend.
 

9

DNA Binding Proteins


•Unique structural ____ are important elements of ___ ___ ____ in transcription factors.
•These regions bind to ___ ____ ___ in the DNA.
____ ___
____ ____
____ ___ ____
___ ___ ___


•Unique structural motifs are important elements of DNA binding domains in transcription factors.
•These regions bind to specific sequence nucleotides in the DNA.
•Zinc fingers, Leucine zippers, Helix-turn-helix and Helix-loop-helix motifs. 
 

10

Regulation of Gene Specific Transcription Factors 


•The ____ of Transcription factors and co-activators – ___ and ____ controls the level of transcription.
•Binding of _____ (Steroids) can ___ or ___ tanscription factors.
_____ of transcription factors via protein kinases (MAP kinases). 
 


•The availability of Transcription factors and co-activators – Synthesis and degradation controls the level of transcription.
•Binding of ligands (Steroids) can activate or inhibit transcription factors.
•Phosphorylation of transcription factors via protein kinases (MAP kinases). 
 

11

 Homeobox Genes (Hox)


•Control ___ ____ _____ & ___ ____ during development in wide variety of organisms (fruit flies to humans).
•encode ____ ____that bind DNA.
•Contains a __ __ ___motif in ___ ___ ___ (_______).
•Determine____particular groups of genes ____ during ___ ___
 


•Control position-specific differentiation & body segmentation during development in wide variety of organisms (fruit flies to humans).
•Transcription factors that bind DNA.
•Contains a helix-turn helix motif in DNA binding domain (homeodomain).
•Determine when particular groups of genes expressed during embryonic development.
 

12

Example Hox Mutations

____deletion

Disruption of the____gene 

Mouse forelimb bones (mutations in 2 genes from Hox-11 group) 

Ubx deletion

Disruption of the Hoxd13 gene 

Mouse forelimb bones (mutations in 2 genes from Hox-11 group) 

13

Transcription Factors Associated with Tooth Development


•Tooth development occurs through a series interactions between the ___ ___ and the ____ during ____.
•Involves ___-____interactions and ____ _____
•Goes through a series of developmental stage beginning with the _____ of the ___ ____.
Followed by ____ of the ____ into a___ and subsequent _____of the ____ to form the ___ and the ___.
•The _____ mesenchyme gets completely ____ by the ____ forming the late

__ stage.
•The epithelium closest to the ____ develops into the___ producing ____, while  the adjacent mesenchyme differentiates into ___ producing ____s. 
 


•Tooth development occurs through a series interactions between the oral epithelium and the mesenchyme during embryogenesis.
•Involves ligand-receptor interactions and transcriptional control.
•Goes through a series of developmental stage beginning with the invagination of the oral epithelium.
•Followed by condensation of the mesenchyme into a bud and subsequent extension of the epithelium to form the Cap and the Bell
•The condensed mesenchyme gets completely surrounded by the epithelium forming the late Bell stage.
•The epithelium closest to the dental mesenchyme develops into the enamel producing ameloblasts, while  the adjacent mesenchyme differentiates into dentin producing odontoblasts. 
 

14

Transcription Factors Associated with Tooth Development


•Several transcription factors are expressed in the _____. These transcription factors are expressed and function at ___ ____ of development, thereby controlling tooth development.
•Loss of any of these factors leads to ______ of tooth development.
•They are involved in the control of ____, ____ and _____ in each stage.
•Example- ___and ___ and ____Homeobox proteins)
 


•Several transcription factors are expressed in the mesenchyme. These transcription factors are expressed and function at specific stages of development, thereby controlling tooth development.
•Loss of any of these factors leads to arrest of tooth development.
•They are involved in the control of cell division, differentiation and apoptosis in each stage.
•Example- Msx1 and Msx2 and Pax9 (Homeobox proteins)
 

15

Abnormalities of Tooth Development Results in Deficiencies in the Expression of Transcription Factors

Hypodontia –

Mutations in ____can lead to arrest of teeth at the___ stage.

Loss or mutations in____ can also causes arrest at the ___ stage. 

Hypodontia – the absence of one to six teeth, excluding third molars.

Mutations in Msx1 can lead to arrest of teeth at the bud stage.

Loss or mutations in Pax9 can also causes arrest at the bud stage. 

16

Post-transcriptional Regulation

___ ___
___ ___
___ ___
______


•Alternative splicing
•RNA editing
•mRNA stability
•microRNA


 

17

Alternate Splicing


•Alternate splicing mechanisms create multiple proteins from a___ gene (____)
_____-specific proteins (liver vs salivary amylase)
____ poorly understood but involves specific ____ ___ ____
 


•Alternate splicing mechanisms create multiple proteins from a single gene (diversity)
•Tissue-specific proteins (liver vs salivary amylase)
•Control poorly understood but involves specific RNA binding proteins

 

18

RNA editing 


•Nucleotides can be___ or ___ while ____ can be altered ___ ____
•Known as RNA editing.
•Occurs in ___ ___
•The same mRNA will ____ from tissue to tissue. 
 


•Nucleotides can be deleted  or added, while bases can be altered after transcription. 
•Known as RNA editing.
•Occurs in different tissues.
•The same mRNA will differ from tissue to tissue. 
 

19

mRNA stability:


•Typical mRNA t 1/2 : ___ - ____
__________ affects stability
•mRNA that encode for ____ ____ most unstable   Ex) ____ ___, ___ ____
•Signal near ___’end-___-rich leads to _____
____ in ___ mRNA’s like ____
 


•Typical mRNA t1/2=30 min-20hr
•Poly-A tail length affects stability
•mRNA that encode for regulatory proteins most unstable
•Growth factors, transcription factors
•Signal near 3’end-AU-rich leads to degradation
•Absent in stable mRNA’s like globin

 

20

MicroRNAs


•Small RNA molecules that are synthesized by ______
•These microRNA molecules ___ or ____translation by binding to the _____________ regions of the target ____ controlling protein expression. mRNA can be ____


•Small RNA molecules that are synthesized by RNA pol II.
•These microRNA molecules inhibit or stall translation by binding to the 3’ un-translated regions of the target mRNA controlling protein expression. mRNA can be degraded. 

21

Summary


•Control of gene regulation is required for altering gene expression during _____ and also to avoid ___ of ___
____ ___ and ___ ____are two important processes in gene regulation.
___ ___ ____ are components that regulate transcription.
•___ ____ ____ ____are important post-transcriptional processes.

 


•Control of gene regulation is required for altering gene expression during development and also to avoid wastage of energy.
•Chromatin modeling and DNA methylation are two important processes in gene regulation.
•Transcription factors, activators and repressors are components that regulate transcription.
•Splicing, RNA editing, polyadenylation and microRNAs are important post-transcriptional processes.