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

Question
How can a complete organism be cloned ?

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

Differentiated cell contains genetic instruction

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

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.

Level of protein controlled by gene expression

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.

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

The Generation of Embryonic Stem Cells after Somatic-Cell Nuclear Transfer

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

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

Cited by 20 international journals until 2011 Websites : www. google.com; www. yahoo.com ; searching : Hadyanto Lim Lim H, YZ Zhu. Cell Mol Life Sci 2006; 63: 2584-96 (Switzerland)

Cited by Other Articles in International Journals

(Printed in USA) (Printed in USA) (Printed in Great Britain)

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

Belmadani S, Bernal J, Chih-Chang Wei CC, et al., American Journal of Pathology 171:777-789. (Sept 2007). University of Alabama, Birmingham (USA)

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

University of Toronto, Toronto, ON, Canada

Cited by Other Articles in International Journals

(Printed in USA) Printed in Oxford University (Great Britain)

Journal of Clinical Hypertension 2008;10: 69-72

Cardiovasc Res 2009; 84: 209-217 Gleen DJ, Rahmutula D, Lionakis N, Moyssakis I, Gialafos E Nishimoto M, Liang F, Cardiology Department, Gardner DG. Laiko General Hospital, University of California, San Athens, Greece Francisco, USA

Eur Heart Fail 2010; 12 : 219-226 Shyu KG et al Taipei Medical University, Taipei, Taiwan

Cited by Other Articles in International Journals

Printed in Netherlands Printed in USA Printed in Germany

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

J Cell Mol Med 2009; 13: 4415-21

Rudolf Jarai et al Department of Cardiology and Emergency Medicine

M. Brueckmann, et al 2010, online Medical Faculty of Mannheim, University of Heidelberg, Germany.

Department of Internal Medicine II, Medical University of Vienna, Austria (Impact Factor: 5.228 ) (IF 2.09)

Cited by Other Articles in International Journals

Printed in USA Printed in USA

Human Gene Therapy 2011; 21 :1545-1554;

YX Zhao et al.
1The

Int J Endocrinol 2010; 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

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.

Cited by Other Articles in International Journals

Printed in Germany Printed in Japan

Cell Tis Res 2011 Transforming growth factor beta signaling in adult cardiovascular diseases and repair Doetschman T, et al. , Univ. Arizona, USA

Circulation J 2011

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

Cited by Other Articles in International Journals

Printed in USA Printed in Spain

Synthesis and biological evaluation of

1-substituted-3-(6-methylpyridin-2-yl)-4-([1,2,4] Transforming growth factor-1 in essential hypertension triazolo[1,5-a]pyridin-6-yl)pyrazoles as Blanco M, et al. transforming growth factor- type 1 receptor Area de biotecnologa, Hospital de Alta Resolucin kinase inhibitors Valle del Guadiato, Pearroya, Crdoba, Espaa Jin CH et al. 2011 College of Pharmacy, Ewha Womans University, Published in Laboratorio Clinico. 2011;04:121-6. vol.04 nm 03 Republic of Korea 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 translationallevel control

The Last

DNA Replication and Repair