GATA transcription factors drive initial Xist upregulation after fertilization through direct activation of a distal enhancer element

To ensure dosage compensation for X-linked genes between the sexes, one X chromosome is silenced during early embryonic development of female mammals. This process of X-chromosome inactivation (XCI) is initiated through upregulation of the RNA Xist from one X chromosome shortly after fertilization. Xist then mediates chromosome-wide gene silencing in cis and remains expressed in all cell types except the germ line and the pluripotent state, where XCI is reversed. The factors that drive Xist upregulation and thereby initiate XCI remain however unknown. We identify GATA transcription factors as potent Xist activators and demonstrate that they are essential for the activation of Xist in mice following fertilization. Through a pooled CRISPR activation screen we find that GATA1 can drive ectopic Xist expression in murine embryonic stem cells (mESCs). We demonstrate that all GATA factors can activate Xist directly via a GATA-responsive regulatory element (RE79) positioned 100 kb upstream of the Xist promoter. Additionally, GATA factors are essential for the induction of XCI in mouse preimplantation embryos, as simultaneous deletion of three members of the GATA family (GATA1/4/6) in mouse zygotes effectively prevents Xist upregulation. Thus, initiation of XCI and possibly its maintenance in distinct lineages of the preimplantation embryo is ensured by the combined activity of different GATA family members, and the absence of GATA factors in the pluripotent state likely contributes to X reactivation. We thus describe a form of regulation in which the combined action of numerous tissue-specific factors can achieve near-ubiquitous expression of a target gene

Two-dimensional gravitation and Sine-Gordon-Solitons

Some aspects of two-dimensional gravity coupled to matter fields, especially to the Sine-Gordon-model are examined. General properties and boundary conditions of possible soliton-solutions are considered. Analytic soliton-solutions are discovered and the structure of the induced space-time geometry is discussed. These solutions have interesting features and may serve as a starting point for further investigations.Comment: 23 pages, latex, references added, to appear in Phys.Rev.

Hypoxia induces a transcriptional early primitive streak signature in pluripotent cells enhancing spontaneous elongation and lineage representation in gastruloids

The cellular microenvironment, together with intrinsic regulators, shapes stem cell identity and differentiation capacity. Mammalian early embryos are exposed to hypoxia in vivo and appear to benefit from hypoxic culture in vitro. Yet, how hypoxia influences stem cell transcriptional networks and lineage choices remain poorly understood. Here, we investigated the molecular effects of acute and prolonged hypoxia on embryonic and extra-embryonic stem cells as well as the functional impact on differentiation potential. We find a temporal and cell type-specific transcriptional response including an early primitive streak signature in hypoxic embryonic stem cells mediated by HIF1α. Using a 3D gastruloid differentiation model, we show that hypoxia-induced T expression enables symmetry breaking and axial elongation in the absence of exogenous WNT activation. When combined with exogenous WNT activation, hypoxia enhances lineage representation in gastruloids, as demonstrated by highly enriched signatures of gut endoderm, notochord, neuromesodermal progenitors and somites. Our findings directly link the microenvironment to stem cell function and provide a rationale supportive of applying physiological conditions in models of embryo development

Unexpectedly small intrashell L1–L3 vacancy transition rate in 62Sm

Stötzel R, Werner U, Sarkar M, Jitschin W. Unexpectedly small intrashell L1–L3 vacancy transition rate in 62Sm. Physical Review A. 1992;45(3):2093-2096

Unexpectedly small intrashell L1−L3\mathrm{L_1 - L_3} vacancy transition rate in 62Sm\mathrm{_{62}Sm}

The individual decay channels of samarium L-subshell vacancy states were experimentally investigated by the synchrotron photoionization method. For the Coster-Kronig yield f13, i.e., the relative contribution of the nonradiative L1−L3 channel to the total decay of L1-vacancy states, the value f13=0.19±0.03 was obtained. This is a surprisingly small value regarding both prediction from theory (e.g., f13=0.32 according to Chen, Craseman, and Mark [Phys. Rev. A 24, 177 (1981)]) and extrapolation from neighboring elements (f13≊0.32 for the elements with Z=72–74 according to our previous work [U. Werner and W. Jitschin, Phys. Rev. A 38, 4009 (1988)])

Exploration of different wave patterns in a model of the bovine estrous cycle by Fourier analysis

Cows typically have different numbers of follicular waves during their hormonal cycle. Understanding the underlying regulations leads to insights into the reasons for declined fertility, a phenomenon that has been observed during the last decades. We present a systematic approach based on Fourier analysis to examine how parameter changes in a model of the bovine estrous cycle lead to different wave patterns. Even without any biological considerations, this allows to detect the responsible model parameters that control the type of periodicity of the solution, thus supporting experimental planning of animal scientists