i want 25 mutiple choice questions with their model answer below each question  that covers different aspects of all of the following information : • Housekeeping gene
- under constitutive expression
- constantly expressed in approximately all cells
Regulated gene
- Levels of the gene product rise and fall with the needs of the organism.
- Such genes are inducible.
⚫ able to be turned on
- Such genes are also repressible.
⚫ able to be turned off
Furthermore, gene regulation drives the processes of cellular differentiation and morphogenesis, leading to the creation of different cell types in multicellular organisms where the different types of cells may possess different gene expression profile. Genes and Regulatory Elements
• Structural genes: encoding proteins
• Regulatory genes: encoding products that interact with other sequences and affect the transcription and translation of these sequences
• Regulatory elements: DNA sequences that are not transcribed but play a role in regulating other nucleotide sequences Gene Expression Prokaryotic vs. Eukaryotic
Prokaryotic cells:
• lack a nuclear envelope
• allows translation to begin while transcription progresses
Eukaryotic cell:
The nuclear envelope
separates transcription from translation
Extensive RNA
processing occurs in the nucleus EPIGENETICS
Reversible heritable chemical modification of DNA or histone or nonhistone proteins that does not alter DNA sequence itself.
The term epigenetics means, above genetics' as the nucleotide sequence is unaltered
This is one of the recently discovered method of regulation of gene expression.
Epigenome: Constellation of covalent modification of DNA and histones that impact chromatin structure and modulation of gene expression.
Epigenetic modifications include
DNA Methylation
Post-translational modification of Histones Biochemical Functions of Epigenetic Modification
1. Regulation of tissue specific gene expression
2. X chromosome inactivation (Facultative Heterochro- matin) one of the two X-chromosomes in every cell of a female
3. Genomic imprinting: Gene inactivation on selected chromosomal regions of autosomes is called Genomic Imprinting. This is the cause of preferential expres- sion of one of the parental allele.
Maternal imprinting refers to transcriptional silencing of the maternal allele.
Paternal imprinting implies that the paternal allele is inactivated.
Imprinting occurs in the ovum or the sperm, before fertilization.
4. Ageing Process DNA methylation:is the addition or removal of a methyl group predominantely where cytosine bases occur consecutively Eukaryotic Regulation
• Controlling the expression of eukaryotic genes requires transcription factors.
general transcription factors are required for transcription initiation
⚫ required for proper binding of RNA polymerase to the DNA
-specific transcription factors increase transcription in certain cells or in response to signals
35 Eukaryotic Transcription
• General transcription factors bind to the promoter region of the gene.
• RNA polymerase II then binds to the promoter to begin transcription at the start site (+1).
• Enhancers are DNA sequences to which specific transcription factors (activators) bind to increase the rate of transcription. 
Gene expression begins with DNA and results in protein
• Gene expression is the process by which genetic instructions are used to synthesize gene products
3Lac operon 467Gene Expression
Prokaryotic vs. Eukaryotic
8An overview of gene expression
9Chromosomal Remodeling
Important Note:
Regulation of Gene Transcription by
Chromosomal Remodeling is called
“Epigenetics”DNA modification by Methylation
(Gene Silencing)
• DNA methylation occurs as a post
replicative modification.
• CH3 groups are added to C bases in CG rich
regions present in the promotor called CG
islandsImportance of DNA Methylation
1. Prevents binding of transcription factors to C bases
of promotor
prevents binding of RNA
Polymerase;
“Gene Silencing”2. Methylated areas attract histone deacetylase
(HDAC) enzyme,
removing acetyl groups from
histones
exposing positive charges of histones
hetero-chromatin
tight binding to DNA forming condensed
inhibition of transcription;
“Gene Silencing”Epigenetic inheritance
• Not controlled by base
sequences.
• DNA methylation
(deactivates one
homologous chromosome)
may explain abnormal or
unexpected DNA
expression as is often seen
in identical twins.Histone Acetylation/ Deacetylation
(Opening DNA)
• The double stranded DNA is folded around
Histones compactly;
“Condensed Heterochromatin”
This is achieved by the action of
“Histone De-acetylase enzyme”• Inorder to allow binding of RNA Polymerase & transcription factors, DNA must be relaxed & opened; “Relaxed Euchromatin”
This is achieved by the action of “Histone Acetylase enzyme”2122Anatomy of a Typical Eukaryotic Gene, with Its Core Promoter and Proximal Control Region
Coordinate regulation The need to coordinately regulate a group of genes to cause a particular response is of key importance in organisms with more than one chromosome. An underlying theme occurs repeatedly: A transacting protein functions as a specific transcription factor (STF) that binds to a cis-acting regulatory consensus sequence on each of the genes in the group even if they are on different chromosomes. Note: Tile STF has a DNA-binding domain (DBD)Enhancers and Silencers
24What are these Sequences?
Enhancer and Silencers are regulatory
sequences on the DNA strand itself & located
away from promotor of a Gene.Enhancer Sequences
Help binding of RNA
This enhancer
Polymerase enzyme to
promotor sequence
sequence is also called
Response element
Enhancer sequence might act
as a binding site for an
external signal coming to the
cell.
Example: hormonal ResponseSilencer Sequences
Can act as
binding site
for Repressor
Molecule
Preventing
binding of RNA
Polymerase to
promotor
Inhibiting
TranscriptionAlternative RNA processing
• Intron-exon splice sites
• Polyadenylation
– eg. Alternative splicing and processing, results in the formation of
seven unique -tropomyosin mRNAs in seven different tissues
282. RNA processing control:
• RNA processing regulates mRNA production from precursor RNAs.
• Two independent regulatory mechanisms occur:
•
Alternative polyadenylation = where the polyA tail is added
•
Alternative splicing
= which exons are spliced
• Alternative polyadenylation and splicing can occur together.mRNA stability
• Turn-over rate very short (~ 30 min)
• The stability of the mRNA can be influenced by
hormones and certain other effectors
• The ends of mRNA molecules are involved in
mRNA stability
– The 5' cap structure in eukaryotic mRNA prevents
attack by 5' exonucleases
– the poly(A) tail prohibits the action of 3‘
exonucleases
30RNA Editing
31RNA Interference
• Small, noncoding RNAs base pair with target
sequences in mRNA like microRNA
• The small RNAs interfere with expression of the
target mRNAs either by repression of translation or
by increased degradationncRNA: 1000’s of RNA’s, current
research
• miRNA’s - micro RNA hat can
degrade mRNA or block
translation
• Causes mRNA to fold on
itself and base pair to create
dsRNA which is then
digested with an enzyme
• Small interferring RNA
(siRNA) – also degrade
mRNA or block translation
(blocking by siRNA is called
RNAi, or RNA interferance)Post-translational control - protein degradation:
• Proteins can be short-lived (e.g., steroid receptors) or long-lived (e.g., lens proteins in your eyes).
• This is a cells last change to affect gene expression.
• Protease, enzymes that break down proteins, are confined to lysosomes and proteasomes.
• When a protein is tagged by a signaling protein, it enters a proteasome to be degraded.