REGULATION

OF
GENE EXPRESSION
 Control of gene expression in
Eukaryotes
• The coding portion of eukarytotic DNA is very small as
compared with non coding.
• The function of extra DNA is unknown.
• The DNA is extensively folded and packed into the protein
DNA complex called chromatin.
• Many processes are involved in control of gene expression.
Hassan
Hassan
Hassan
Gene Control in Eukaryotes

In eukaryotic cells, the ability to express biologically

active proteins comes under regulation at several
points:
 1. Chromatin Structure:
• The physical structure of DNA in the chromatin, can
affect the ability of transcription factors and RNA
polymerases to find access to specific genes and to
activate transcription from them.
• For example, the DNA containing the β-globin gene
cluster is in “active”chromatin (euchromatin). in
the reticulocyte but in “inactive” chromatin
(heterochromatin ) in muscle cells.
• These mechanisms are methylation of cytidine
residues in the DNA that are found in the
dinucleotide, CG (most often written as a CpG ) and
histone modification.

• The term epigenetics is used to define the

mechanism by which changes in the pattern of
inherited gene expression occur in the absence of
alterations or changes in the nucleotide composition
of a given gene e.g. methylation.
2. Transcriptional Initiation:
• This is the most important mode for control of
eukaryotic gene expression. Specific factors that exert
control include enhancers & inhibitors which
affect activity of RNA polymerase at a given promoter
by binding specific transcription factors.
• Enhancer elements differ from the promoter in
two remarkable ways. They can exert their positive
influence even when separated by thousands of base
pairs from a promoter, and they may act on more
than one promoter.
Motifs of protein binding to DNA :

Specificity involved in the control of transcription

requires that regulatory proteins bind with high
affinity to the correct region of DNA. Three unique
motifs emerge :
Helix-Loop-Helix (HLH)

Zinc Fingers

Leucine Zipper
3. Transcript Processing :

Eukaryotic mRNAs are modified before being

active. Several genes have been identified that
undergo tissue-specific patterns of alternative
splicing, which generate biologically different
proteins from the same gene.
4. RNA Transport:
• A fully processed mRNA must leave the nucleus in
order to be translated into protein.
• So by altering transport pattern we alter gene
expression.
5. Transcript Stability:
• Unlike prokaryotic mRNAs, whose half-lives are all in
the range of 1--5 minutes, eukaryotic mRNAs can vary
greatly in their stability.
•mRNA exist in the cytoplasm in association with
porteins as ribonucleoprotein particles (RNPs).
•It is thought that mRNAs are stabilized or destabilized
by the interaction of proteins with these RNPs
protiens.
6. Translational Initiation:
•Since many mRNAs have multiple methionine
codons, the ability of ribosomes to recognize and
initiate synthesis from the correct AUG codon can
affect the expression of a gene product.
• Several examples have emerged demonstrating that
some eukaryotic proteins initiate at non-AUG
codons. This phenomenon has been known to
occur in E. coli for quite some time, but only
recently has it been observed in eukaryotic mRNAs.
7. Post-Translational Modification:

•Common modifications include glycosylation,

acetylation, fatty acylation, disulfide bond formations,
etc.
 8. Protein Transport:

• In order for proteins to be biologically active

following translation and processing, they must be
transported to their site of action.
9. Control of Protein Stability:

•Many proteins are rapidly degraded, whereas others

are highly stable. Specific amino acid sequences in
some proteins have been shown to bring about rapid
degradation.
10. Small RNAs and Control of Transcript
Levels:
•snRNA-mediated control can be exerted either at the
level of the translatability of the mRNA, the stability of
the mRNA or via changes in chromatin structure.
•As recently as 15 years ago it was believed that the only
non-coding RNAs were the tRNAs and the rRNAs.
However, in a landmark study published in 1993 on the
control of developmental timing in the roundworm
Caenorhabditis elegans it was shown that the control of
one gene was exerted by the small non-coding RNA
product of another gene.
Hassan