Transcription &

Modification

Maria Julinarus Presto Gumalo

Connie D. Salipsip

MSTB - II
Gene regulation makes cells different
• Gene regulation is how a cell
controls which genes, out of the
many genes in its genome, are
"turned on" (expressed). 

Example: The jobs of the liver is to

remove toxic substances like
alcohol from the bloodstream.
 How do cells "decide" which genes to turn on?
Gene expression pattern is determined by information from both inside and
outside the cell.
• Examples of information from inside the cell: the proteins it inherited
from its mother cell, whether its DNA is damaged, and how much ATP
it has.

• Examples of information from outside the cell: chemical signals from

other cells, mechanical signals from the extracellular matrix, and
nutrient levels.

They have molecular pathways that convert information – such as the

binding of a chemical signal to its receptor – into a change in gene
expression.
 How do cells "decide" which genes to turn on?

A growth factor is a
chemical signal from a
neighboring cell that
instructs a target cell to
grow and divide. 
Gene regulation makes cells different
Steps involves in eukaryotic gene expression

• Chromatin accessibility. The structure of chromatin

(DNA and its organizing proteins) can be regulated.
More open or “relaxed” chromatin makes a gene more
available for transcription.
• Transcription. Transcription is a key regulatory point
for many genes. Sets of transcription factor proteins
bind to specific DNA sequences in or near a gene and
promote or repress its transcription into an RNA.
• RNA processing. Splicing, capping, and addition of a
poly-A tail to an RNA molecule can be regulated, and so
can exit from the nucleus. Different mRNAs may be
made from the same pre-mRNA by alternative splicing.
Gene regulation makes cells different
Steps involves in eukaryotic gene expression

• RNA stability. The lifetime of an mRNA molecule in

the cytosol affects how many proteins can be made
from it. Small regulatory RNAs called miRNAs can
bind to target mRNAs and cause them to be chopped
up.
• Translation. Translation of an mRNA may be increased
or inhibited by regulators. For instance, miRNAs
sometimes block translation of their target mRNAs
(rather than causing them to be chopped up).
• Protein activity. Proteins can undergo a variety of
modifications, such as being chopped up or tagged with
chemical groups. These modifications can be regulated
and may affect the activity or behavior of the protein. Image based on similar diagrams from Reece et al. ^111, Purves et al. ^22
 Transcription Factors
Transcription is the process where a gene's DNA sequence is copied (transcribed) into
an RNA molecule. 

Gene expression is when a gene in DNA is "turned on," that is, used to make the protein it
specifies. Not all the genes in your body are turned on at the same time, or in the same cells or
parts of the body.

For many genes, transcription is the key on/off control point:

1. If a gene is not transcribed in a cell, it can't be used to make a protein in that cell.
2. If a gene does get transcribed, it is likely going to be used to make a protein (expressed). In
general, the more a gene is transcribed, the more protein that will be made.
Proteins called transcription factors, however, play a particularly central role in regulating
transcription. 
Transcription Factors
How do transcription factors work?
Activators
How do transcription factors work?
Repressors
How do transcription factors work?
Binding sites
How is this different from E. coli?

Humans and other eukaryotes are

complex: we're made up of trillions
of cells organized into unique tissues
and body structures. Each cell in
your body must run its own
"program" of gene expression.
 Turning genes on in specific body parts
Example: Modular mouse

A gene with this type of pattern

may have
several enhancers (far-away
clusters of binding sites for
activators) or silencers (the
same thing, but for repressors).

Not drawn fully to scale. Image based on Figure 5 of Menke et al.^33

Transcription factors and cellular "logic"
Regulation After Transcription
Key points:
Even after a gene has been
Some transcripts can
transcribed, gene
undergo alternative
01 expression can still be
regulated at various
02 splicing, making different
mRNAs and proteins from
stages.
the same RNA transcript.

Some mRNAs are targeted A protein's activity may be

03 by microRNAs, small 04 regulated after translation, for
example, through removal of
regulator RNAs that can cause
an mRNA to be chopped up or amino acids or addition of
block translation. chemical groups.
Regulation After Transcription
Gene expression can also be regulated, including:

● RNA processing, such as splicing, capping, and poly-A tail addition

● Messenger RNA (mRNA) translation and lifetime in the cytosol
● Protein modifications, such as addition of chemical groups
Regulation After Transcription
Regulation of RNA processing

Alternative splicing

This allows either of two (or more) mRNA molecules to be made from one
pre-mRNA.

Image modified from "

Eukaryotic Post-transcriptional Gene Regulation: Figure 1," by
OpenStax College, Biology (CC BY 3.0).
Regulation After Transcription
Small regulatory RNAs

A recently discovered class of

regulators, called small regulatory
RNAs, can control mRNA lifespan and
translation. 

microRNAs
microRNAs (miRNAs) were among the
first small regulatory RNAs to be
discovered. A miRNA is first transcribed as
a long RNA molecule, 
Regulation After Transcription
Regulation of translation

Image credit: "Eukaryotic translational and post-translational gene regulation," by OpenStax College,
Biology, CC BY 4.0
Regulation After Transcription
Proteins can be regulated after translation
Phosphorylation
One of the most common post-translational
modifications is phosphorylation, in which a
phosphate group is attached to a protein. 
Regulation After Transcription
Proteins can be regulated after translation
Ubiquitination

Proteins can be tagged for degradation

by the addition of a chemical marker
called ubiquitin. Ubiquitin-tagged
proteins are taken to the proteasome,
or “recycling center” of the cell, and
broken down into their component
parts.

Image credit: "

Eukaryotic translational and post-translational gene regulation: Figure
2
," by OpenStax College, Biology CC BY 4.0
References
Gilbert, S. F. (2000). Anatomy of the gene: Promoters and enhancers. In Developmental biology (6th ed.).
Sunderland, MA: Sinauer Associates. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK10023/#_A751_.

Gilbert, S. F. (2000). Silencers. In Developmental biology (6th ed.). Sunderland, MA: Sinauer Associates.
Retrieved from http://www.ncbi.nlm.nih.gov/books/NBK10023/#_A777_.

Menke, D. B., Guenther, C., and Kingsley, D. M. (2008). Dual hindlimb control elements in the Tbx4 gene and
region-specific control of bone size in vertebrate limbs. Development, 135, 2543-2553. 
http://dx.doi.org/10.1242/dev.017384.

Wray, Gregory A. (2007). The evolutionary significance of cis-regulatory mutations. Nature Reviews

Genetics, 8, 206-216. http://dx.doi.org/10.1038/nrg2063.

Reece, J. B., Urry, L. A., Cain, M. L., Wasserman, S. A., Minorsky, P. V., and Jackson, R. B. (2011).
Combinatorial control of gene activation. In Campbell Biology (10th ed., pp. 37). San Francisco, CA: Pearson.

Reményi, Attila, Hans R. Schöler, and Matthias Wilmanns. (2004). Combinatorial control of gene
expression. Nature Structural & Molecular Biology, 11(9), 812. http://dx.doi.org/10.1038/nsmb820. Retrieved
from http://www.nature.com/scitable/content/Combinatorial-control-of-gene-expression-16976 .
References
Reece, J. B., Urry, L. A., Cain, M. L., Wasserman, S. A., Minorsky, P. V., and Jackson, R. B.
(2011). Figure 18.6. Stages in gene expression that can be regulated in eukaryotic cells.

In Campbell Biology (10th ed., p. 365). San Francisco, CA: Pearson.

Purves, W. K., Sadava, D. E., Orians, G. H., and Heller, H.C. (2003). Figure 14.11.
Potential points for the regulation of gene expression in eukaryotes. In Life: The science of
biology (7th ed., p. 290). Sunderland, MA: Sinauer Associates.

Kimball, John W. (2014, April 19). The human and chimpanzee genomes. In Kimball's
biology pages. Retrieved from http://www.biology-pages.info/H/HominoidClade.html.