Pleiotropic Functions for Transcription Factor Zscan10

Kraus, Petra; Sivakamasundari,; Yu, Hong; Xing, Xing; Lim, Siew Lan; Adler, Thure; Pimentel, Juan Antonio Aguilar; Becker, Lore; Bohla, Alexander; Garrett, Lillian; Hans, Wolfgang; Hölter, Sabine M.; Janas, Eva; Moreth, Kristin; Prehn, Cornelia; Puk, Oliver; Rathkolb, Birgit; Rozman, Jan; Adamski, Jerzy; Bekeredjian, Raffi; Busch, Dirk H.; Graw, Jochen; Klingenspor, Martin; Klopstock, Thomas; Neff, Frauke; Ollert, Markus; Stoeger, Tobias; Yildrim, Ali Önder; Eickelberg, Oliver; Wolf, Eckhard; Wurst, Wolfgang; Fuchs, Helmut; Gailus‐Durner, Valérie; Angelis, Martin Hrabé de; Lufkin, Thomas; Stanton, Lawrence W.

doi:10.1371/journal.pone.0104568

Cited by 19 publications

(15 citation statements)

References 62 publications

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“…loss-of-function mutation exhibited pleiotropic outcomes, affecting numerous physiological systems including but not limited to the renal, cardiovascular, respiratory, and the immune systems (Kraus et al, 2014). However, there have yet to be any reports of the functional consequences of Zscan10 overexpression, and as such the link to embryonic growth identified in this chapter is novel.…”

Section: Discussionmentioning

confidence: 80%

“…Zscan10 is best known for its role in regulating embryonic stem cell development (Zhang et al, 2006), but it has been proposed that it may continue to regulate progenitor cells for the remainder of embyronic development and postnatal life (Kraus et al, 2014). Mice homozygous for a Zscan10…”

Section: Discussionmentioning

confidence: 99%

“…Many (Ptx3, Epha5, Bcl11b, Dcx, Phlda2, Cdx1, Zscan10, and Ddr2) had a known association with a growth phenotype, though often this was reported postnatally rather than prenatally (Chawengsaksophak et al, 1997;Katsuragi et al, 2013;Kraus et al, 2014;Labrador et al, 2001;Mamiya et al, 2008;Tunster et al, 2014;Werner et al, 2012;Witasp et al, 2014). The presence of genes with known roles in growth in our list provided assurance that the filtering conducted was valid, and that the resultant gene list was likely to be involved in the growth phenotype.…”

Section: Differentially Expressed Genes In Ethanol-exposed Male Embryosmentioning

confidence: 99%

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A study of the consequences of early gestational ethanol and/or nicotine exposure in the mouse

Yamada¹

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The in utero environment is a critical determinant of the immediate and future health of the developing fetus. In Australia, two of the most commonly used drugs during pregnancy are alcohol and nicotine. Prolonged periods of gestational exposure to alcohol and nicotine, separately, have been associated with a range of adverse outcomes in the offspring, in both humans and experimental animal models. The consequences of ethanol and nicotine exposure restricted to early gestation on resultant offspring are poorly characterised, and few animal models exist to build greater understanding. Moreover, the immediate molecular changes associated with exposures to ethanol and/or nicotine restricted to early gestation has yet to be described.This thesis utilised mouse models of early gestational ethanol and/or nicotine exposure to explore the impact of each of these exposures on offspring growth, as well as their associated transcriptional and epigenetic changes. In each model, pregnant C57BL/6 dams were provided with ad libitum access to solutions of 10% ethanol and/or 100 µg/ml nicotine from fertilisation (0.5 dpc) to midgestation (8.5 dpc). The exposure window utilised in each of the models is developmentally equivalent to the first three to four weeks of a human pregnancy.Previously, our laboratory identified reduced growth, microcephaly, and gene expression changes in the liver and hippocampus of the postnatal offspring of the model of prenatal ethanol exposure utilised in this thesis. In contrast, at mid-gestation (9.5 dpc), there was no evidence of developmental delay (somite number), reduced growth (crown-rump length), or microcephaly.Further, a genome-wide gene expression microarray (targeting 30 855 genes) and a screen of the expression of 641 microRNAs, identified only one gene (Bcl11b) as differentially expressed in male 9.5 dpc whole embryos following the ethanol exposure. These data suggest that there is a delay between the ethanol exposure and the onset of adverse phenotypes -arguing that the embryo is somehow able to form a memory of the ethanol exposure. The absence of widespread transcriptional changes suggests that changes in embryonic mRNA and microRNA expression are unlikely to be major contributors to the memory of the exposure.A early gestational model of nicotine exposure was newly established in this thesis. This nicotine exposure resulted in an average serum cotinine (metabolite of nicotine) concentration similar to that reported in humans who smoke 10 to 15 cigarettes per day. This exposure was sufficient to induce a reduction in body size both at mid-gestation and postnatally, but not at late gestation. Furthermore, the increased expression of Zscan10 in the whole male 9.5 dpc embryo was identified and validated across multiple cohorts. Zscan10 encodes for a transcription factor expressed throughout development, with a proposed role in the regulation of progenitor cells. The increased expression of Zscan10 in the nicotine-exposed embryos was associated with a reduction in DNA methylation ...

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Section: Discussionmentioning

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Section: Differentially Expressed Genes In Ethanol-exposed Male Embryosmentioning

confidence: 99%

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A study of the consequences of early gestational ethanol and/or nicotine exposure in the mouse

Yamada¹

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“…As such, we may be detecting the impression left by a protein on the structure of DNA, several decades after the fact (Ziller et al, 2015). To that end, there is evidence supporting a role for ZSCAN10 in maintaining a multipotent progenitor cell population in mid-gestation embryos and adult organs (Kraus et al, 2014).…”

Section: Discussionmentioning

confidence: 97%

Cell-type specific open chromatin profiling in human postmortem brain infers functional roles for non-coding schizophrenia loci

Fullard

Giambartolomei

Hauberg

et al. 2016

Preprint

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To better understand the role of cis regulatory elements in neuropsychiatric disorders we applied ATAC-seq to neuronal and non-neuronal nuclei isolated from frozen postmortem human brain. Most of the identified open chromatin regions (OCRs) are differentially accessible between neurons and non-neurons, and show enrichment with known cell type markers, promoters and enhancers. Relative to those of non-neurons, neuronal OCRs are more evolutionarily conserved and are enriched in distal regulatory elements. Our data reveals sex differences in chromatin accessibility and identifies novel OCRs that escape X chromosome inactivation, with implications for intellectual disability.Transcription factor footprinting analysis identifies differences in the regulome between neuronal and non-neuronal cells and ascribes putative functional roles to 16 non-coding schizophrenia risk variants.These results represent the first analysis of cell-type-specific OCRs and TF binding sites in postmortem human brain and further our understanding of the regulome and the impact of neuropsychiatric disease-associated genetic risk variants.3

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“…In addition, it was also reported that Zscan10 might act as a transcriptional activator of the 2-cell-stage specific transcripts, such as Zscan4 and Tcstv1, because their expression levels are decreased in Zscan10 knocked-down ES cells [5]. In contrast, it was recently reported that Zscan10 knockout mice can develop to adult organisms although they have some defects such as weight reduce or eye defect [9], suggesting that its function for the maintenance of the pluripotent cell population in early developmental process is either dispensable or masked by the maternal transcripts. In the previous reports that applied shRNA-mediated knock-down strategy for the loss of function experiments, 10-20% of total Zscan10 transcripts still remained [4,5].…”

Section: Introductionmentioning

confidence: 99%

Zscan10 is dispensable for maintenance of pluripotency in mouse embryonic stem cells

Yamane¹,

Fujii²,

Ohtsuka³

et al. 2015

Biochemical and Biophysical Research Communications

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Zinc finger and SCAN domain-containing 10 (Zscan10, also known as Zfp206) encodes a transcription factor that has been reported to be involved in the maintenance of pluripotency in mouse embryonic stem (ES) cells. Here we generated inducible knockout ES cells for Zscan10 using the Cre-loxP system and analyzed its function. We succeeded in establishing Zscan10-null ES cells and confirmed their pluripotency by the generation of chimeric embryos. Our results clearly indicate that Zscan10 is dispensable for the ability of self-renewal and differentiation in ES cells.

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Pleiotropic Functions for Transcription Factor Zscan10

Cited by 19 publications

References 62 publications

A study of the consequences of early gestational ethanol and/or nicotine exposure in the mouse

A study of the consequences of early gestational ethanol and/or nicotine exposure in the mouse

Cell-type specific open chromatin profiling in human postmortem brain infers functional roles for non-coding schizophrenia loci

Zscan10 is dispensable for maintenance of pluripotency in mouse embryonic stem cells

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