Gene expression and its regulation in Prokayotes and Eukaryotes. It explains the key processes involved in regulating the intricate activity.

1. GENE EXPRESSION
AND REGULATION
By: David Enoma
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2. GENE EXPRESSION
◦It is a complex process involving coordination of dynamic events,
which are subject to regulation at multiple levels.
◦It is an important process to develop various biological functions
and drive the phenotypes
◦The process by which information encoded in a gene leads to the
production of a protein (Wang & Cheng, 2018)
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3. GENE EXPRESSION
◦The majority of human genes thus consist of a long string
of alternating exons and introns, with most of the gene
consisting of introns.
◦In addition to introns and exons, each gene is associated with
regulatory DNA sequences, which are responsible for
ensuring that the gene is turned on or off at the proper time,
expressed at the appropriate level, and only in the proper
type of cell.
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4. GENE EXPRESSION
◦Unvarying expression of a gene is called constitutive gene
expression.
◦For other gene products, cellular levels rise and fall in
response to molecular signals; this is regulated gene
expression.
◦The regulation of transcription initiation often entails
changes in how RNA polymerase interacts with a
promoter(Nelson & Cox, 2012). 4

5. DNA TRANSLATION
◦Translation is the last step in gene expression, during which the
coding sequence of mRNA is translated into the amino-acid
sequence of a protein.
◦It entails four major phases: initiation, elongation, termination,
and ribosome recycling (Rodnina, 2018)
◦Translational control is an important contributor to regulating
gene expression and many disease states occur because of its
dysfunction (Hershey et al., 2019)
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6. REGULATION OF GENE
EXPRESSION
◦Regulation of gene expression includes a wide range of
mechanisms that are used by cells to increase or decrease the
production of specific gene products (protein or RNA).
◦There can be positive, negative and double negative
regulation.
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7. WHY REGULATION OF GENE
EXPRESSION
◦Enables the cell to conserve energy and resources.
◦By switching genes off when they are not needed, cells can
prevent resources from being wasted.
◦Allows the cell to respond efficiently to environmental
conditions.
◦It increases the versatility and adaptability of an organism
by allowing the cell to express protein when needed.
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8. ◦Gives a cell control over its structure and function.
◦It drives cell differentiation & morphogenesis processes
resulting in different cell types in multicellular organisms.
◦Cells of complex multicellular organisms switch genes on
and off during development.
◦A typical human cell normally expresses about 3% to 5% of
its genes at any given time.
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9. PROKARYOTIC GENE EXPRESSION
◦In Prokaryotic gene expression, the basal level of
transcription is determined by the effect of promoter
sequences
◦The gene cluster and promoter, plus additional sequences
that function together in regulation, are called an operon
(Nelson & Cox, 2012)
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10. PATTERNS OF REGULATION OF
TRANSCRIPTION INITIATION
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11. PROTEINS REGULATING
TRANSCRIPTION
◦At least three types of proteins regulate transcription
initiation by RNA polymerase:
◦Specificity factors alter the specificity of RNA polymerase
for a given promoter
◦Repressors impede access of RNA polymerase to the
promoter.
◦Activators enhance the RNA polymerase–promoter
interaction
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12. Induction of the SOS Response
◦Extensive DNA damage in the bacterial chromosome
triggers the induction of many distantly located genes.
◦The key regulatory proteins are the RecA protein and the
LexA repressor
◦ Induction of the SOS response requires removal of LexA
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13. Figure 1: SOS response in E. coli (Nelson & Cox, 2012)
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14. Induction of the SOS Response
◦DNA damage leads to numerous single-strand gaps in the
DNA, and only RecA that is bound to single-stranded DNA
can facilitate cleavage of the LexA repressor
◦Binding of RecA at the gaps eventually activates its
coprotease activity, leading to cleavage of the LexA repressor
and SOS induction
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15. Figure 2: An Oscillatory Behavior for the SOS Response (Michel, 2005)
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16. TRYPTOPHAN OPERON
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17. EUKARYOTIC GENE REGULATION
◦For eukaryotes, cell-cell differences are determined by
expression of different sets of genes. For instance, an
undifferentiated fertilized egg looks and acts quite different
from a skin cell.
◦Eukaryotic gene regulation relies on protein-protein
interactions and combinatorial interactions.
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19. 19

20. REGULATION OF
TRANSCRIPTIONAL INITIATION
◦DNA-binding transcription factors (TFs) are key regulators
of gene expression.
◦Although their structural and functional heterogeneity makes
it difficult to group them into distinct categories.
◦Each TF has a specific DNA binding domain that recognizes
a 6-10 base-pair motif in the DNA, as well as an effector
domain.
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21. REGULATION OF TRANSCRIPTION AT
GENES OF GALACTOSE METABOLISM
IN YEAST
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22. TRANSCRIPTIONAL CONTROL
◦For transcription to occur, the area around a prospective
transcription zone needs to be unwound.
◦This is a complex process requiring the coordination of
histone modifications, transcription factor binding and other
chromatin remodeling activities.
◦Heterochromatin vs Euchromatin
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23. Pre-mRNA processing control
◦Capping, splicing and polyA tail addition
◦Splicing is removal of the intervening intron sequences that
are present between the exon coding sequences of
transcripts.
◦Polyadenylation starts is catalyzed by poly(A) polymerase
that binds the growing end of the poly(A) tail (Stewart,
2019)
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24. The gene expression pathway from transcription to
translation for budding yeast
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25. TRANSLATIONAL REGULATION
CONTROL
◦mRNA levels obviously play a role in determining the amounts of
protein produced by the translational machinery.
◦mRNA levels are determined by their rates of transcription and
processing, but also by their rates of transport into the cytoplasm.
◦Also by their rates of degradation that may be coupled to or
influenced by their translation (Heck & Wilusz, 2018)
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26. RNA STABILITY CONTROL
◦Si-RNA can stimulate the degradation of mRNAs (Hershey
et al., 2019)
◦MicroRNAs also cause RNA interference to occur.
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27. RNA INTERFERENCE
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28. ◦Some of the small RNA molecules that induce RNAi are
derived from the transcripts of microRNA genes. These
genes, usually denoted by the symbol mir, are found in the
genomes of many kinds of eukaryotes
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29. OTHER TRANSCRIPTIONAL CONTROLS
◦Imprinting is yet another process involved in eukaryotic gene
regulation; this process involves the silencing of one of the
two alleles of a gene for a cell's entire life span (Lyon, 1994).
◦Protein modification, transport and stability
◦Imprinted gene expression is subsequently maintained using
noncoding RNAs, histone modifications, insulators, and
higher-order chromatin structure (Bartolomei, 2009).
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30. PROTEIN MODIFICATION
◦Each type of histone is subject to enzymatic modification by
methylation,acetylation, ADP-ribosylation, phosphorylation,
glycosylation, sumoylation,or ubiquitination.
◦Such modifications affect the net electric charge, shape, and
other properties of histones, as well as the structural and
functional properties of the chromatin.
◦they play a role in the regulation of transcription of genes
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31. X-Inactivation
◦ X inactivation. In female mammals, for instance, one of the
two copies of the X chromosome is shut off and compacted
greatly.
◦This shutoff process requires transcription, the participation
of two noncoding RNAs (one of which coats the inactive X
chromosome)
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32. REFERENCES
◦ Nelson, D. L., & Cox, M. M. (2012). Lehninger Principles of Biochemistry: 6th Edition. Macmillan Learning.
◦ Wang, D., & Cheng, C. (2018). Genomics and Systems Biology. In Cooperative and Graph Signal Processing
(pp. 725–733). Elsevier. https://doi.org/10.1016/b978-0-12-813677-5.00027-4
◦ Bartolomei, M. S. (2009). Genomic imprinting: Employing and avoiding epigenetic processes. In Genes
and Development (Vol. 23, Issue 18, pp. 2124–2133). Cold Spring Harbor Laboratory Press.
https://doi.org/10.1101/gad.1841409
◦ Heck, A. M., & Wilusz, J. (2018). The interplay between the RNA decay and translation machinery in
eukaryotes. Cold Spring Harbor Perspectives in Biology, 10(5), a032839.
https://doi.org/10.1101/cshperspect.a032839
◦ Hershey, J. W. B., Sonenberg, N., & Mathews, M. B. (2019). Principles of translational control. Cold
Spring Harbor Perspectives in Biology, 11(9), a032607. https://doi.org/10.1101/cshperspect.a032607
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33. REFERENCES
◦ Lyon, M. F. (1994). The X inactivation centre and X chromosome imprinting. In European Journal of
Human Genetics (Vol. 2, Issue 4, pp. 255–261). Nature Publishing Group.
https://doi.org/10.1159/000472369
◦ Michel, B. (2005). After 30 years of study, the bacterial SOS response still surprises us. In PLoS Biology
(Vol. 3, Issue 7, pp. 1174–1176). Public Library of Science.
https://doi.org/10.1371/journal.pbio.0030255
◦ Nelson, D. L., & Cox, M. M. (2012). Lehninger Principles of Biochemistry: 6th Edition. Macmillan Learning.
https://books.google.com.ng/books?id=n9e1NAEACAAJ
◦ Rodnina, M. V. (2018). Translation in prokaryotes. In Cold Spring Harbor Perspectives in Biology (Vol. 10,
Issue 9, p. a032664). Cold Spring Harbor Laboratory Press.
https://doi.org/10.1101/cshperspect.a032664
◦ Wang, D., & Cheng, C. (2018). Genomics and Systems Biology. In Cooperative and Graph Signal Processing
(pp. 725–733). Elsevier. https://doi.org/10.1016/b978-0-12-813677-5.00027-4
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