Cover Page
The handle http://hdl.handle.net/1887/39295 holds various files of this Leiden University dissertation
Author: Polman, J.A.E.
Title: Glucocorticoid signature in a neuronal genomic context
Issue Date: 2016-05-10
Glucocorticoid Signature Neuronal Genomic Context in a
Japke Anne Elisabeth Polman
Glucocorticoid Signature in a Neuronal Genomic Context Japke Anne Elisabeth Polman
Thesis, Leiden University May 10, 2016
ISBN: 978-94-6299-326-6
Cover design: J.A.E. Polman & M.A. Groeneweg Layout: M.A. Groeneweg
Printing: Ridderprint BV, www.ridderprint.nl
© J.A.E. Polman
No part of this thesis may be reproduced or transmitted in any form or by any means without written permission of the author.
Glucocorticoid Signature Neuronal Genomic Context in a
Proefschrift
ter verkrijging van
de graad van Doctor aan de Universiteit Leiden, op gezag van Rector Magnificus prof. mr. C.J.J.M. Stolker,
volgens besluit van het College voor Promoties te verdedigen op dinsdag 10 mei 2016
klokke 16:15 uur
door
Japke Anne Elisabeth Polman Geboren te Gouda in 1980
Promotor Prof. dr. E.R. de Kloet Co-promotor Dr. N.A. Datson
Leden promotiecommissie Prof. dr. S.M. van der Maarel
Prof. dr. P.J. Lucassen (University of Amsterdam) Prof. dr. G.J. Martens (Radboud University, Nijmegen) Prof. dr. O.C. Meijer
Prof. dr. P.E. Slagboom Dr. E. Vreugdenhil
The studies described in this thesis were performed at the Department of Medical Pharma- cology of the Leiden Academic Centre for Drug Research (LACDR) and Leiden University Medical Center (LUMC), the Netherlands. This research was financially supported by grants from the Netherlands Organization for Scientific Research (NWO) (836.06.010), Top Insti- tute (TI) Pharma (T5-209), Human Frontiers of Science Program (HFSP) (RGP39) and the Royal Netherlands Academy of Arts and Sciences (KNAW).
Voor Erik,
mijn onvoorwaardelijke steun
List of Abbreviations
AF Activation Function
CA Cornu Ammonis
ChIP Chromatin Immunoprecipitation ChIP-seq ChIP-sequencing
CORT Cortisol or Corticosterone
DBD DNA-Binding Domain
DG Dentate Gyrus
GBS Glucocorticoid Receptor Binding Site
GCs Glucocorticoids
GR Glucocorticoid Receptor
GRE Glucocorticoid Response Element HPA-axis Hypothalamic-Pituitary-Adrenal axis
LBD Ligand Binding Domain
MR Mineralocorticoid Receptor
mTOR mammalian Target of Rapamycin
nGRE negative GRE
NTD N-terminal Transactivation Domain
RT-qPCR Real-time Quantitative Polymerase Chain Reaction
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Contents
1 General introduction . . . . 1
2 Specific regulatory motifs predict glucorticorticoid responsiveness of hippocampal gene expression . . . . 23
3 A genome-wide signature of glucocorticoid receptor binding in neuronal PC12 cells . . . . 53
4 Two populations of glucocorticoid receptor-binding sites in the male rat hippocampal genome . . . 83
5 Glucocorticoids modulate the mTOR pathway in the hippocampus: differential effects depending on stress history . . . . 107
6 General Discussion . . . 131
7 Summary . . . 147
8 Samenvatting . . . 155
References . . . 161
Curriculum Vitae . . . 184
Publication list . . . 185
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