@article{WittFrankGillesetal.2018, author = {Witt, Stephanie H. and Frank, Josef and Gilles, Maria and Lang, Maren and Treutlein, Jens and Streit, Fabian and Wolf, Isabell A. C. and Peus, Verena and Scharnholz, Barbara and Send, Tabea S. and Heilmann-Heimbach, Stefanie and Sivalingam, Sugirthan and Dukal, Helene and Strohmaier, Jana and S{\"u}tterlin, Marc and Arloth, Janine and Laucht, Manfred and N{\"o}then, Markus M. and Deuschle, Michael and Rietschel, Marcella}, title = {Impact on birth weight of maternal smoking throughout pregnancy mediated by DNA methylation}, series = {BMC genomics}, volume = {19}, journal = {BMC genomics}, publisher = {BMC}, address = {London}, issn = {1471-2164}, doi = {10.1186/s12864-018-4652-7}, pages = {10}, year = {2018}, abstract = {Background: Cigarette smoking has severe adverse health consequences in adults and in the offspring of mothers who smoke during pregnancy. One of the most widely reported effects of smoking during pregnancy is reduced birth weight which is in turn associated with chronic disease in adulthood. Epigenome-wide association studies have revealed that smokers show a characteristic "smoking methylation pattern", and recent authors have proposed that DNA methylation mediates the impact of maternal smoking on birth weight. The aims of the present study were to replicate previous reports that methylation mediates the effect of maternal smoking on birth weight, and for the first time to investigate whether the observed mediation effects are sex-specific in order to account for known sex-specific differences in methylation levels. Methods: Methylation levels in the cord blood of 313 newborns were determined using the Illumina HumanMethylation450K Beadchip. A total of 5,527 CpG sites selected on the basis of evidence from the literature were tested. To determine whether the observed association between maternal smoking and birth weight was attributable to methylation, mediation analyses were performed for significant CpG sites. Separate analyses were then performed in males and females. Results: Following quality control, 282 newborns eventually remained in the analysis. A total of 25 mothers had smoked consistently throughout the pregnancy. The birthweigt of newborns whose mothers had smoked throughout pregnancy was reduced by >200g. After correction for multiple testing, 30 CpGs showed differential methylation in the maternal smoking subgroup including top "smoking methylation pattern" genes AHRR, MYO1G, GFI1, CYP1A1, and CNTNAP2. The effect of maternal smoking on birth weight was partly mediated by the methylation of cg25325512 (PIM1); cg25949550 (CNTNAP2); and cg08699196 (ITGB7). Sex-specific analyses revealed a mediating effect for cg25949550 (CNTNAP2) in male newborns. Conclusion: The present data replicate previous findings that methylation can mediate the effect of maternal smoking on birth weight. The analysis of sex-dependent mediation effects suggests that the sex of the newborn may have an influence. Larger studies are warranted to investigate the role of both the identified differentially methylated loci and the sex of the newborn in mediating the association between maternal smoking during pregnancy and birth weight.}, language = {en} } @article{GillesOttoWolfetal.2018, author = {Gilles, Maria and Otto, Henrike and Wolf, Isabell A. C. and Scharnholz, Barbara and Peus, Verena and Schredl, Michael and Suetterlin, Marc W. and Witt, Stephanie H. and Rietschel, Marcella and Laucht, Manfred and Deuschle, Michael}, title = {Maternal hypothalamus-pituitary-adrenal (HPA) system activity and stress measures at birth}, series = {Psychoneuroendocrinology}, volume = {94}, journal = {Psychoneuroendocrinology}, publisher = {Elsevier}, address = {Oxford}, issn = {0306-4530}, doi = {10.1016/j.psyneuen.2018.04.022}, pages = {152 -- 161}, year = {2018}, abstract = {Background: Prenatal maternal stress might be a risk for the developing fetus and may have long-lasting effects on child and adult vulnerability to somatic and psychiatric disease. Over-exposure of the unborn to excess glucocorticoids and subsequent alteration of fetal development is hypothesized to be one of the key mechanisms linking prenatal stress with negative child outcome. Methods: In this prospective longitudinal study, mothers-to-be (n = 405) in late pregnancy (36.8 +/- 1.9 weeks of gestational age) and their singleton neonates were studied. We investigated the impact of different prenatal stress indices derived from six stress variables (perceived stress, specific prenatal worries, negative life events, symptoms of depression, trait anxiety, neuroticism) and diurnal maternal saliva cortisol secretion on gestational age and anthropometric measures at birth.}, language = {en} } @article{SendGillesCoddetal.2017, author = {Send, Tabea Sarah and Gilles, Maria and Codd, Veryan and Wolf, Isabell and Bardtke, Svenja and Streit, Fabian and Strohmaier, Jana and Frank, Josef and Schendel, Darja and Suetterlin, Mark W. and Denniff, Matthew and Laucht, Manfred and Samani, Nilesh J. and Deuschle, Michael and Rietschel, Marcella and Witt, Stephanie H.}, title = {Telomere Length in Newborns is Related to Maternal Stress During Pregnancy}, series = {Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology}, volume = {42}, journal = {Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology}, publisher = {Nature Publ. Group}, address = {London}, issn = {0893-133X}, doi = {10.1038/npp.2017.73}, pages = {2407 -- 2413}, year = {2017}, abstract = {Telomere length (TL) is a marker of biological aging, and numerous studies have shown associations between TL and somatic or psychiatric disorders. Research also indicates an association between maternal stress during pregnancy and TL in the offspring. The present study investigated possible associations between TL and: (1) maternal perceived stress during pregnancy; (2) a maternal lifetime history of psychiatric disorder (lifetime PD); and (3) paternal age. TL was analyzed in 319 newborns and 318 mothers from a predominantly Caucasian sample (n= 273 Caucasian newborns and n= 274 Caucasian mothers). Two key findings were observed. First, maternal perceived stress during pregnancy was associated with shorter telomeres in newborns but not with maternal TL. Second, maternal lifetime PD was associated with shorter maternal telomeres, but not with TL in newborns. Paternal age was not associated with TL in newborns. The finding that maternal stress during pregnancy is associated with shorter telomeres in newborns supports the results of smaller previous studies. The fact that a relation between maternal prenatal stress and TL was observed in the offspring but not in mothers may be attributable to a high vulnerability to stress during intrauterine development of a maturing organism. To our knowledge, this is the largest study to date to show that maternal stress during pregnancy but not maternal lifetime PD is associated with shorter telomeres in the offspring.}, language = {en} } @article{WittZanorMuellerRoeber2004, author = {Witt, Isabell and Zanor, Maria Ines and M{\"u}ller-R{\"o}ber, Bernd}, title = {Transcription factor function search : how do individual factors regulate agronomical important processes in plants? (Subproject A)}, isbn = {3-00-011587-0}, year = {2004}, language = {en} } @article{SkiryczReicheltBurowetal.2006, author = {Skirycz, Aleksandra and Reichelt, Michael and Burow, Meike and Birkemeyer, Claudia Sabine and Rolcik, Jacub and Kopka, Joachim and Zanor, Maria Ines and Gershenzon, Jonathan and Strnad, Miroslav and Szopa, Jan and M{\"u}ller-R{\"o}ber, Bernd and Witt, Isabell}, title = {DOF transcription factor AtDof1.1 (OBP2) is part of a regulatory network controlling glucosinolate biosynthesis in Arabidopsis}, year = {2006}, abstract = {Glucosinolates are a group of secondary metabolites that function as defense substances against herbivores and micro-organisms in the plant order Capparales. Indole glucosinolates (IGS), derivatives of tryptophan, may also influence plant growth and development. In Arabidopsis thaliana, indole-3-acetaldoxime (IAOx) produced from tryptophan by the activity of two cytochrome P450 enzymes, CYP79B2 and CYP79B3, serves as a precursor for IGS biosynthesis but is also an intermediate in the biosynthetic pathway of indole-3-acetic acid (IAA). Another cytochrome P450 enzyme, CYP83B1, funnels IAOx into IGS. Although there is increasing information about the genes involved in this biochemical pathway, their regulation is not fully understood. OBP2 has recently been identified as a member of the DNA-binding-with-one- finger (DOF) transcription factors, but its function has not been studied in detail so far. Here we report that OBP2 is expressed in the vasculature of all Arabidopsis organs, including leaves, roots, flower stalks and petals. OBP2 expression is induced in response to a generalist herbivore, Spodoptera littoralis, and by treatment with the plant signalling molecule methyl jasmonate, both of which also trigger IGS accumulation. Constitutive and inducible over- expression of OBP2 activates expression of CYP83B1. In addition, auxin concentration is increased in leaves and seedlings of OBP2 over-expression lines relative to wild-type, and plant size is diminished due to a reduction in cell size. RNA interference-mediated OBP2 blockade leads to reduced expression of CYP83B1. Collectively, these data provide evidence that OBP2 is part of a regulatory network that regulates glucosinolate biosynthesis in Arabidopsis}, language = {en} }