Control of Gene Expression

Prof. DR. dr. Hadyanto Lim, M.Kes, SpFK, FESC, FIBA

Department of Pharmacology and Molecular Sciences
Faculty of Medicine, Methodist University of Indonesia - Medan
Molecular Biology Research, Postgraduate School,
University of Sumatra Utara - Medan

How can a complete
organism be cloned ?
Question
Wilmut I.et al. Nature 1997; 385: 810-13.

A differentiated cell contains all the genetic instructions
necessary to direct the formation of a complete organism
Differentiated cell contains genetic instruction


Cell differentiation generally depends on
changes in gene expression
Because the tadpole contain a full range of differentiated
cell that derive their DNA sequences from the nucleus of the
original donor cell, it follows that the differentiated donor
cell cannot have lost any important DNA sequence.
Differentiated cell contains genetic instruction
Differentiated cell contains genetic instruction
Cell type
Different cell types synthesize different sets of protein,
but many processes are common to all cells. These
include :
1. Structural proteins of chromosomes,
2. RNA polymerases
3. DNA repair enzymes
4. Ribosomal proteins
5. Enzymes involved in the central reactions of
metabolism
6. Proteins that form the cytoskeleton
Control of gene expression in eukaryote
Level of protein controlled by gene expression
1. Transcriptional control, controlling when and
how often a given gene is transcribed.
2. RNA proccessing control, controlling the splicing
and processing of RNA transcripts.
3. RNA transport and localization control,
selecting which completed mRNAs are exported
from the nucleus to the cytosol and determining
where in the cytosol they are localized.

4. Translational control, selecting which RNAs in
the cytoplasm are translated by ribosomes.
5. mRNA degradation control, selectively
destabilizing certain mRNA molecules in the
cytoplasm.
6. Protein activity control, selectively activating,
inactivating, degrading, or localizing specific
protein molecules after they have been made.

Level of protein controlled by gene expression
Functional role of miRNAs
in the normal and
diseased heart
Small EM, & Olson EN. Nature 2011; 469:
336-342
Levels of Control of Gene Expression

Human Cloning
Snyder E , Loring J. N Engl J Med 2006;354:321-324
The Generation of
Embryonic Stem Cells
after Somatic-Cell Nuclear
Transfer
The US President Position on Human Cloning
On April 10, 2002, President Bush
announced that he believed that all
human cloning is wrong and that
therefore both reproductive cloning and
research cloning ought to be banned.




Anna GI. N Eng J Med 2002; 346: 1599-1602.
Why the heart transforms

Lim H, YZ Zhu. Cell Mol Life Sci 2006; 63: 2584-2596 (Switzerland).
Review Article
Lim H, YZ Zhu. Cell Mol Life Sci 2006; 63: 2584-96 (Switzerland)
Websites : www. google.com; www. yahoo.com ; searching : Hadyanto Lim

Cited by 20 international journals until 2011
Cited by Other Articles in International Journals
Belmadani S, Bernal J,
Chih-Chang Wei CC, et al.,
American Journal of
Pathology 171:777-789.
(Sept 2007).

University of Alabama,
Birmingham (USA)

Prud'homme GJ
Laboratory Investigation
87:1077-1091.
(Aug 2007).


University of Toronto,
Toronto, ON, Canada
Grobe JL ,
Der Sarkissian S. Stewart
JM et al,. Clinical Science
113 :357-364.
(Oct 2007).

University of Florida,
Gainesville (USA)



(Printed in Great Britain) (Printed in USA) (Printed in USA)
Cited by Other Articles in International Journals
Journal of Clinical
Hypertension 2008;10: 69-72

Lionakis N, Moyssakis I, Gialafos E
Cardiology Department,
Laiko General Hospital,
Athens, Greece
Cardiovasc Res 2009; 84:
209-217
Eur Heart Fail 2010; 12 :
219-226
Gleen DJ, Rahmutula D,
Nishimoto M, Liang F,
Gardner DG.


Shyu KG et al
(Printed in USA) Printed in Oxford University (Great Britain)
University of California, San
Francisco, USA
Taipei Medical University,
Taipei, Taiwan
Cited by Other Articles in International Journals
Heart Fail Rev 2010; 15:133142
Pol CJ, Muller A, Simonides WS
Department of Physiology, Institute
for Cardiovascular Research,
VU University Medical Center
Amsterdam 1081 BT,
The Netherlands
Printed in Netherlands
Rudolf Jarai et al
Department of Cardiology and
Emergency Medicine

Department of Internal Medicine II,
Medical University of Vienna,
Austria (Impact Factor: 5.228 ) (IF 2.09)
J Cell Mol Med 2009; 13: 4415-21
Printed in USA
M. Brueckmann, et al
2010, online
Medical Faculty of
Mannheim,
University of Heidelberg,
Germany.
Printed in Germany
Cited by Other Articles in International Journals
1
The Key Laboratory of Cardiovascular Remodeling
and Function Research, Chinese Ministry of
Education and Chinese Ministry of Health,
Shandong University Qilu Hospital, Jinan,
Shandong, 250012, China.
Human Gene Therapy 2011; 21 :1545-1554;
YX Zhao et al.
Diniz, Gabriela Placon
Laboratory of Cellular Biology and
Functional Anatomy, Department of
Anatomy, Institute of Biomedical
Sciences, University of So Paulo,
05508-900, So Paulo, Brazil
Int J Endocrinol 2010;
Printed in USA Printed in USA
Cell Tis Res 2011
Transforming growth factor beta
signaling in adult cardiovascular
diseases and repair
Doetschman T, et al. ,
Univ. Arizona, USA
Cited by Other Articles in International Journals
Relationship Between Myocardial Redox State
and Matrix Metalloproteinase Activity in
Patients on Left Ventricular Assist Device
Support

Caruso R et al.
1

CNR Clinical Physiology Institute, Cardiovascular
Department, Niguarda C Granda Hospital
Milan, Italy

Printed in Japan Printed in Germany
Circulation J 2011
Synthesis and biological evaluation of
1-substituted-3-(6-methylpyridin-2-yl)-4-([1,2,4]
triazolo[1,5-a]pyridin-6-yl)pyrazoles as
transforming growth factor- type 1 receptor
kinase inhibitors
Jin CH et al. 2011
College of Pharmacy, Ewha Womans University,
Republic of Korea

Printed in USA
Transforming growth factor-1 in essential
hypertension
Blanco M, et al.
Area de biotecnologa, Hospital de Alta Resolucin
Valle del Guadiato, Pearroya, Crdoba, Espaa

Published in Laboratorio Clinico. 2011;04:121-6. -
vol.04 nm 03
Spain


Cited by Other Articles in International Journals
Printed in Spain
Kompas, January 5, 2006

Dr. Hadyanto Lim, MSc, PhD, a senior lecturer at the School of Medicine, Methodist
University of Indonesia, described the role of TGF-1 in postinfarction cardiac
remodeling in heart failure.
Control of Gene Expression in Prokaryotes
Promoter is a specific DNA sequence that directs RNA polymerase to
bind to DNA, to open the DNA double helix, and to begin synthesizing
an RNA molecule.
Operator, a regulator element within the promoter that directs
transcription.
Control of Gene Expression in Prokaryotes
Organization of a Bacterial Operon (cluster of genes that code for enzyme)

Transcription of the
structural genes is
controlled by a
repressor protein
that, when bound to
the operator site of
the DNA, blocks
movement of the
RNA polymerase
from the promoter to
the structural genes
Switching the triptophan genes on and off
The binding of tryptophan to the tryptophan
repressor protein changes its conformation
The mechanism of gene regulatory proteins that control
gene transcription in procaryotes
Processing Level Control

The fibronectin gene consists
of a number of exons.
Two of these exons encode
portions of the polypeptide
called EIIIA and EIIIB, which
are included in the protein
produced fibroblasts, but
which are excluded from the
protein produced in the liver.
Fibronectin produced by
fibroblasts are retained in
the matrix contains two extra
peptides compared to the
version of the protein
produced by liver cells and
secreted into the blood.


The difference is due to alternative splicing.
Translation-Level Control

The Untranslated
regions (UTRs) contain
nucleotide sequences
used by the cell to
mediate translational-
level control
The Last


DNA Replication and Repair