• Eukaryotic Regulation Regulation of Gene Expression – Part II Spring 2013 - Althoff Reference: Mader & Windelspecht Ch. 13) Lec 19
Jan 05, 2016
• Eukaryotic Regulation
Regulation of Gene Expression – Part IISpring 2013 - Althoff Reference: Mader & Windelspecht Ch. 13)
Lec19
• With few known exceptions….____________ of a multicellular eukaryote has a complete complement of genes.
• Cell type differences (i.e., muscle vs. nerve vs. liver vs. etc.) result because only a certain set of genes is “___________” in the ___________…thus, a different set of proteins are “active” in the cytoplasm.
• There are 5 primary levels of control: 3 pertain to the __________, 2 of them pertain to the _____________
Eukaryotic Regulation
• Chromatin Structure – in the nucleus
• Transcriptional Control – in the nucleus
• Posttranscriptional Control – in the nucleus
• Translational Control — in the cytoplasma
• Posttranslational Control – in the cytoplasma
Eukaryotic Regulation – 5 types of control
1
2
3
4
5
1
2
3
4
5
Nucleus
Cytoplasma
• Chromatin packing is used as a way to keep genes turned ____. If genes are not accessible to ________________, they cannot be ___________.
•
• Chromatin structure is one method of __________ ___________ = transmission of genetic information “__________” the ______________ of a gene.
• Chromatin is a “stringy” variety of proteins material… most prevalent during interphase of the cell cycle
Type: Chromatin Structure
1
• One class of DNA-associated proteins are ____________. They play an important role in ________________ of DNA.
• Without histones, DNA could not fit inside the nucleus. Each human cell contains about 2 meters of DNA…yet the nucleus is only 5-8 цm in diameter.
• _______________ chromatin = ______________
• _______________ chromatin = ______________
Type: Chromatin Structure
1
Nucleus with staining showing…heterochromatin and euchromatin
nucleolus
DNA Unpacking
1
_____________ promoter
chromatin remodeling
nucleosome
___________ promoter
DNA to be __________3
2
• Heterochromatin is not transcribed…
• Heterochromatin does not permit access by RNA polymerase
• Genes contained by heterochromatin __________ _______ get transcribed…therefore they are not expressed
• Example: Barr body in mammalian females (XX): chromatin adheres to inner edge of the nuclear membrane—resulting in one inactive X chromosome (i.e., produces no products)
Type: Chromatin Structure
1
• __________ Inheritance: sometimes caused by histone modification…changes that result not in sequence of DNA nucleotides.
• Epigenetic inheritance term is not restricted to the genes themselves causing variation.
•
• Epigenetic inheritance may explain unusual patterns of inheritance …and may play a role in growth, aging, and cancer.
Type: Chromatin Structure
1
• This is considered the _____________ of the 5 control levels
• Keep in mind that the first step towards transcript is availability of DNA
• A eukaryote may have many different types of _________________—proteins that help regulate transcription by assisting RNA polymerase to bind to the _______________.
• There may be __________________ transcription factor active at a single promoter…thus, the absence of one can prevent transcription from taking place
Type: Transcriptional Control
2
• Even with all transcription factors present, transcription might not begin without the presence of a DNA-binding protein called a _____________ ______________
• Transcription activators bind to regions of the DNA called _______________.
• Enhancers may not be located near promoters…
• “Distance” reduced with _____________ in the DNA
Type: Transcriptional Control
2
enhancer
transcriptionactivator
_________________________
1
2
3
• Occurs in the nucleus
• Includes alternative mRNA splicing and controlling of the _____ with which mRNA leaves the nucleus
• During pre-mRNA splicing, ________ (non-coding regions) are excised…and ________ (expressed regions) are joined together to form an mRNA.
• Result: if an exon is _________, it may be is excised along with flanking introns…the result…
• ….the ___________ has an altered sequence and the protein it encoded is altered
• Example: in thyroid, a slightly different calcitonin than what the hypothalamus produces.
Type: Posttranscriptional Control
3
Protein product 1 Protein product 2
wh
at h
app
ens
in t
he
cyto
pla
sma
wh
at h
app
ens
in t
he
nu
cleu
s
• Occurs in the cytoplasma
• Happens __________ a protein product is made
• Associated with activity of the mRNA for translation at the ______________
• Affected by the presence…or…absence… of the 5’ cap and the length of the poly-A (i.e., adenine nucleotide) tail at the 3’ end…this can affect the whether a) __________________…or for _____ _____ the mRNA is active.
• Example: persistence 5’ end caps and long 3’ poly-A tails long-life of mRNAs that code for hemoglobin in mammalian red blood cells
Type: Translational Control
4
• Occurs in the cytoplasma
• Begins once the __________________________ and become active.
• It represents the last chance the cell has for influencing gene expression
• This highlights the fact that not all proteins are “active” after synthesis. Value of this: a protein is only activated when it is appropriate to do so. Example: bovine proinsulin is “held” as such before special bonding process that results in “active” insulin.
Type: Posttranslational Control
5
• Length of time a protein remains active in a cell usually regulated by ____________ = enzymes that breakdown proteins.
• Proteases usually confined to ____________ or special structures called _________________.
Type: Posttranslational Control
5
• For a protein to enter a proteasome, it has to be “tagged” with a signaling protein recognized by the proteasome’s cap.
• When the cap recognizes the tag, it opens up and allows the protein to enter the core of the structure where it is ___________________________.
• This is gene expresssion control” because it regulates the amount of protein product in the cytoplasma
Type: Posttranslational Control
5
5 Posttranslational Control: “________”
Which leads to ________ into proteasomewhere…
5 Posttranslational Control: “___________”
…break down to _______________________.
In summary….
DNAtranscription
mRNAtranslation
protein
modification of DNA via
transcriptional
chromatin structure
posttranscriptional
translational
posttranslational