Control of Gene Expression (FK UMI)

8/13/2019 Control of Gene Expression (FK UMI)

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Control of Gene Expression

Prof. DR. dr. Hadyanto Lim, M.Kes, SpFK, FESC, FIBADepartment of Pharmacology and Molecular Sciences

Faculty of Medicine, Methodist University of Indonesia - Medan

Molecular Biology Research, Postgraduate School,

University of Sumatra Utara - Medan


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How can a completeorganism be cloned ?

Question

Wilmut I.et al. Nature1997; 385: 810-13.
http://www.time.com/time/magazine/0,9263,7601970310,00.html


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A differentiated cell contains all the genetic instructions

necessary to direct the formation of a complete organism


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Differentiated cell contains genetic instruction

Cell differentiation generally depends on

changes in gene expression


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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.



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Cell type

Different cell types synthesize different sets of protein,but many processes are common to all cells. Theseinclude :

1. Structural proteins of chromosomes,

2. RNA polymerases

3. DNA repair enzymes

4. Ribosomal proteins

5. Enzymes involved in the central reactions ofmetabolism

6. Proteins that form the cytoskeleton


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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.


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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


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Functional role of miRNAsin the normal and

diseased heart

Small EM, & Olson EN. Nature 2011; 469:336-342


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Levels of Control of Gene Expression


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Human Cloning


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Snyder E , Loring J. N Engl J Med 2006;354:321-324

The Generation ofEmbryonic Stem Cells

after Somatic-Cell NuclearTransfer


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The US President Position on Human Cloning

On April 10, 2002, President Bush

announced that he believed that all

human cloning is wrongand thattherefore both reproductive cloning and

research cloning ought to be banned.

Anna GI. N Eng J Med2002; 346: 1599-1602.


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Why the heart transforms

Lim H, YZ Zhu. Cell Mol Life Sci 2006; 63: 2584-2596 (Switzerland).


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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


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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)


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Journal of ClinicalHypertension 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


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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, onlineMedical Faculty of

Mannheim,

University of Heidelberg,

Germany.

Printed in Germany


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1The 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


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Cell Tis Res 2011Transforming growth factor beta

signaling in adult cardiovascular

diseases and repair

Doetschman T, et al. ,

Univ. Arizona, USA


Relationship Between Myocardial Redox Stateand 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 HospitalMilan, Italy

Printed in JapanPrinted in Germany

Circulation J 2011
http://www.jstage.jst.go.jp/browse/circj/75/10/_contents


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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

hypertensionBlanco 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


Printed in Spain


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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 cardiacremodeling in heart failure.


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Control of Gene Expression in Prokaryotes

Promoter is a specific DNA sequence that directs RNA polymerase tobind to DNA, to open the DNA double helix, and to begin synthesizing

an RNA molecule. Operator, a regulator element within the promoter that directstranscription.


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Control of Gene Expression in ProkaryotesOrganization 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 tothe operator site of

the DNA, blocks

movement of the

RNA polymerasefrom the promoter to

the structural genes


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Switching the triptophan genes on and off


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The binding of tryptophan to the tryptophan

repressor protein changes its conformation

The mechanism of gene regulatory proteins that control


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The mechanism of gene regulatory proteins that control

gene transcription in procaryotes


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Processing Level Control

The fibronectin gene consistsof a number of exons.

Two of these exons encode

portions of the polypeptide

called EIIIA and EIIIB, which

are included in the proteinproduced 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.


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Translation-Level Control

The Untranslated

regions (UTRs) contain

nucleotide sequences

used by the cell tomediate translational-

level control


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The Last

DNA Replication and Repair

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Control of Gene Expression (FK UMI)

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