University of Groningen

Modifications of collagen and chromatin in ECM-related diseaseGjaltema, Rutger Almer Friso

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Citation for published version (APA):Gjaltema, R. A. F. (2016). Modifications of collagen and chromatin in ECM-related disease: Uncoveringtherapeutic targets for fibrosis and cancer. [Groningen]: Rijksuniversiteit Groningen.

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Rutger Almer Friso Gjaltema

2016

Modifications of collagen and chromatin in ECM-related disease

Uncovering therapeutic targets for fibrosis and cancer

The research in this thesis was performed at the Graduate School of Medical Sciences (GSMS) at the University of Groningen.

This Ph.D project was financially supported by:Netherlands Institute of Regenerative MedicineDutch Kidney FoundationStichting de Cock-Hadders

Modifications of chromatin and collagen in ECM-related disease: Uncovering therapeutic targets for fibrosis and cancer

Gjaltema, R.A.F.

Proefschrift Groningen

ISBN (printed): 978-90-367-9195-3ISBN (digital): 978-90-367-9194-6

Cover design: Rutger A.F. GjaltemaLay-out: Rutger A.F. Gjaltema

Printed by: Ipskamp drukkers

Printing of this thesis was kindly supported by:University of GroningenUniversity Medical Center Groningen

© Copyright 2016 R.A.F. GjaltemaAll rights reserved. No part of this thesis may be reproduced, stored on a retrieval system, or transmitted in any form or by any means, without written permission of the author.

Modifications of collagen and chromatin in ECM-related disease

Uncovering therapeutic targets for fibrosis and cancer

Proefschrift

ter verkrijging van de graad van doctor aan deRijksuniversiteit Groningen

op gezag van de rector magnificus prof. dr. E. Sterken

en volgens besluit van het College voor Promoties.

De openbare verdedigen zal plaatsvinden op

woensdag 9 november 2016 om 14:30 uur

door

Rutger Almer Friso Gjaltema

geboren op 29 maart 1982te Zwolle

PromotoresProf. dr. R.A. BankProf. dr. M.G. Rots

BeoordelingscommissieProf. dr. F.J. Dekker Prof. dr. H. van GoorProf. dr. G.J.V.M. van Osch

Paranimfen:Bram PiersmaMendel Kaelen

Voor mijn vader

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Contents

Chapter 1: Introduction and aims

PARt I: NOVEL FEAtURES OF COLLAGEN MODIFYING ENZYMES

Chapter 2: Molecular Insights Into Prolyl And Lysyl Hydroxylation Of Fibrillar Collagens In Health And Disease

Chapter 3: Disentangling Mechanisms Involved In Collagen Pyridinoline Cross-linking: The Immunophilin FKBP65 Is Critical For Dimerization Of Lysyl Hydroxylase 2

Chapter 4: Lysyl hydroxylase 2 splice variants are chromatin-associated proteins that regulate transcription of target genes

PARt II: tRANSCRIPtIONAL REGULAtION OF PRO-FIBROtIC PROCESSES

Chapter 5: Procollagen Lysyl Hydroxylase 2 Expression is Regulated by an Alternative Downstream Transforming Growth Factor Beta-1 Activation Mechanism

Chapter 6: Enhancer of zeste homolog-2 (EZH2) methyltransferase regulates transgelin/smooth muscle-22 alpha expression in endothelial cells in response to interleukin-1 beta and transforming growth factor-beta 2

Chapter 7: Targeting TET methylcytosine dioxygenases induces a wide spectrum of anti-fibrotic effects

PARt III: tRANSCRIPtIONAL MODULAtION BY tARGEtED REwRItING OF thE EPIGENOME

Chapter 8: KRAB-induced heterochromatin is more effective than targeted DNA methylation in achieving efficient and mitotically stable gene repression

Chapter 9: Writing of H3K4Me3 permanently overcomes silencing in a context-dependent manner

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Chapter 10: Summary & general discussion

Chapter 11: Nederlandse samenvatting

Appendices:AbbreviationsCurriculum vitae and list of publicationsDankwoord

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