Until recently it was thought that small differences in the DNA could
largely explain the way we are. For example, each of us has a slightly
different body shape and more sinister, a different likelihood to get a
disease such as cancer or diabetes. “It’s all in the genes” was the
assumption. We now know that the DNA sequence of an individual does not
tell the whole story.
Gene-environment interactions: Epigenetic systems sense and mark changes
at chromosomal loci. Our laboratory is in the process of exploring how
environmental stimuli and stresses shape the “epigenome” – the
epigenetic state of a cell. We are particularly interested in
DNA methylation. The conceptual framework of our research program is
based on growing evidence that environmental factors influence some
epigenetic programming during critical stages of early life —
programming in early life affects the disease risk in adult life.
To study the phenomenon of fetal programming, a variety of different
approaches are being taken. These include animal model organisms,
gene-specific and genome-wide epigenetic analysis, cell culture systems,
and biochemical assays. With this multi-pronged
strategy we are able to address basic biological questions, which are
relevant to human and animal health.
The questions are: when and how is epigenetic information established,
maintained, removed, and influenced by environmental factors?
Research currently supported by:
Leptin
Leptin (Lep) is a central regulator of energy homeostasis. We have detected highly variable densities of cytosine methylation by hairpin-bisulfite PCR among cells in human adipose tissue and peripheral blood leukocytes.
The thrifty epigenotype
This hypothesis provides an explanation for the difficulty of identifying allelic variations associated with non-syndromic obesity and type 2 diabetes. The hypothesis predicts that small, genome-wide epigenetic changes modulate metabolic networks. Such epigenetic modifications have the potential to be inherited through the germ line – across generations.
Honeybees
Why are honeybees and other insect pollinators declining in number? Could it be that environmental stresses cause subtle changes in RNA transcription that affect the health and behaviour of pollinating insects? We are currently exploring this idea in collaboration with a local beefarmer. More information will follow soon.
Publications
Stöger R, Genereux DP, Hagerman RJ,
Hagerman PJ, Tassone F, Laird CD.
Testing the FMR1 Promoter for Mosaicism in DNA Methylation among
CpG Sites, Strands, and Cells in FMR1-Expressing Males with Fragile X
Syndrome. PLoS One. 2011;6(8):e23648. Epub 2011 Aug
31.
Fertey J, Ammermann I,
Winkler M, Stöger R, Iftner T, Stubenrauch F.
Interaction of the papillomavirus E8--E2C
protein with the cellular CHD6 protein contributes to transcriptional
repression. J Virol. 2010
Sep;84(18):9505-15.
A Q Fu, D P Genereux, R
Stöger, C D Laird,
and M Stephens.
Statistical inference of transmission fidelity of DNA
methylation patterns over somatic cell divisions in mammals.
Annals of Applied Statistics, 2010; 4(2): 871-92.
Voutsinas GE, Stavrou
EF, Karousos G, Dasoula A, Papachatzopoulou A, Syrrou M, Verkerk AJ, van
der Spek P, Patrinos GP, Stöger R, Athanassiadou A.
Allelic imbalance of expression and
epigenetic regulation within the alpha-synuclein wild-type and
p.Ala53Thr alleles in Parkinson disease.
Hum Mutat. 2010 Jun;31(6):685-91.
Lathrop MJ, Chakrabarti
L, Eng J, Rhodes CH, Lutz T, Nieto A, Liggitt HD, Warner S, Fields J,
Stöger R, Fiering S.
Deletion of the Chd6 exon 12 affects motor
coordination. Mamm
Genome. 2010 Apr;21(3-4):130-42.
Stöger R.
Epigenetics and obesity.
Pharmacogenomics. 2008 Dec;9(12):1851-60. Review.
Genereux DP, Johnson WC,
Burden AF, Stöger R, Laird CD.
Errors in the bisulfite conversion of DNA: modulating
inappropriate- and failed-conversion frequencies.
Nucleic Acids Res. 2008 Dec;36(22):e150.
Stöger R.
The thrifty epigenotype: an acquired and
heritable predisposition for obesity and diabetes?
Bioessays. 2008 Feb;30(2):156-66.
McCloskey ML, Stöger R,
Hansen RS, Laird CD.
Encoding PCR products with batch-stamps and
barcodes. Biochem Genet.
2007 Dec;45(11-12):761-7.
Lutz T, Stöger R, Nieto
A.
CHD6 is a DNA-dependent ATPase and localizes
at nuclear sites of mRNA synthesis.
FEBS Lett. 2006 Oct 30;580(25):5851-7.
Stöger R.
In vivo methylation patterns of the leptin
promoter in human and mouse.
Epigenetics. 2006 Oct-Dec;1(4):155-62.
Miner BE, Stöger RJ,
Burden AF, Laird CD, Hansen RS.
Molecular barcodes detect redundancy and contamination in
hairpin-bisulfite PCR. Nucleic Acids Res. 2004 Sep
30;32(17):e135.
Tischkowitz MD, Morgan
NV, Grimwade D, Eddy C, Ball S, Vorechovsky I, Langabeer S, Stöger R,
Hodgson SV, Mathew CG.
Deletion and reduced expression of the Fanconi anemia FANCA gene
in sporadic acute myeloid leukemia. Leukemia. 2004
Mar;18(3):420-5.
Laird CD, Pleasant ND,
Clark AD, Sneeden JL, Hassan KM, Manley NC, Vary JC Jr, Morgan T, Hansen
RS, Stöger R.
Hairpin-bisulfite PCR: assessing epigenetic
methylation patterns on complementary strands of individual DNA
molecules. Proc Natl Acad
Sci U S A. 2004 Jan 6;101(1):204-9.
Schuster EF, Stöger R.
CHD5 defines a new subfamily of
chromodomain-SWI2/SNF2-like helicases.
Mamm Genome. 2002 Feb;13(2):117-9.
Hansen RS, Stöger R,
Wijmenga C, Stanek AM, Canfield TK, Luo P, Matarazzo MR, D'Esposito M,
Feil R, Gimelli G, Weemaes CM, Laird CD, Gartler SM.
Escape from gene silencing in ICF syndrome:
evidence for advanced replication time as a major determinant.
Hum Mol Genet. 2000 Nov 1;9(18):2575-87.
Kispert A, Stöger RJ,
Caparros M, Herrmann BG.
The mouse Rsk3 gene maps to the Leh66
elements carrying the t-complex responder Tcr.
Mamm Genome. 1999 Aug;10(8):794-802.
Tapscott SJ, Klesert TR,
Widrow RJ, Stöger R, Laird CD.
Fragile-X syndrome and myotonic dystrophy: parallels and
paradoxes. Curr Opin Genet Dev. 1998
Apr;8(2):245-53. Review.
Stöger R, Kajimura TM,
Brown WT, Laird CD.
Epigenetic variation illustrated by DNA methylation patterns of
the fragile-X gene FMR1. Hum Mol Genet. 1997
Oct;6(11):1791-801.
Wong DJ, Barrett MT,
Stöger R, Emond MJ, Reid BJ.
p16INK4a promoter is hypermethylated at a high frequency in
esophageal adenocarcinomas. Cancer Res. 1997 Jul
1;57(13):2619-22.
Smrzka OW, Faé I, Stöger
R, Kurzbauer R, Fischer GF, Henn T, Weith A, Barlow DP.
Conservation of a maternal-specific methylation signal at the
human IGF2R locus. Hum Mol Genet. 1995
Oct;4(10):1945-52.
Stöger R, Kubicka P, Liu
CG, Kafri T, Razin A, Cedar H, Barlow DP.
Maternal-specific methylation of the imprinted mouse Igf2r locus
identifies the expressed locus as carrying the imprinting signal.
Cell. 1993 Apr 9;73(1):61-71.
Barlow DP, Stöger R,
Herrmann BG, Saito K, Schweifer N.
The mouse insulin-like growth factor type-2
receptor is imprinted and closely linked to the Tme locus.
Nature. 1991 Jan 3;349(6304):84-7.