Marta Teperek

Nuclear Wave1 Is Required for Reprogramming Transcription in Oocytes and for Normal Development

Egg WAVE1 Eggs not only activate sperm nuclei for normal development but also reprogram transplanted somatic nuclei. In addition to its well-established cytoplasmic role in actin organization, Miyamoto et al. (p. 1002) discovered that the Wiskott-Aldrich syndrome protein family member 1 in oocytes cooperates with transcriptional machineries in the nucleus to activate previously silenced genes. A cytoskeletal protein associates with the transcription machinery and is required for nuclear reprogramming. Eggs and oocytes have a remarkable ability to induce transcription of sperm after normal fertilization and in somatic nuclei after somatic cell nuclear transfer. This ability of eggs and oocytes is essential for normal development. Nuclear actin and actin-binding proteins have been shown to contribute to transcription, although their mode of action is elusive. Here, we find that Xenopus Wave1, previously characterized as a protein involved in actin cytoskeleton organization, is present in the oocyte nucleus and is required for efficient transcriptional reprogramming. Moreover, Wave1 knockdown in embryos results in abnormal development and defective hox gene activation. Nuclear Wave1 binds by its WHD domain to active transcription components, and this binding contributes to the action of RNA polymerase II. We identify Wave1 as a maternal reprogramming factor that also has a necessary role in gene activation in development.

Sperm is epigenetically programmed to regulate gene transcription in embryos

For a long time, it has been assumed that the only role of sperm at fertilization is to introduce the male genome into the egg. Recently, ideas have emerged that the epigenetic state of the sperm nucleus could influence transcription in the embryo. However, conflicting reports have challenged the existence of epigenetic marks on sperm genes, and there are no functional tests supporting the role of sperm epigenetic marking on embryonic gene expression. Here, we show that sperm is epigenetically programmed to regulate embryonic gene expression. By comparing the development of sperm- and spermatid-derived frog embryos, we show that the programming of sperm for successful development relates to its ability to regulate transcription of a set of developmentally important genes. During spermatid maturation into sperm, these genes lose H3K4me2/3 and retain H3K27me3 marks. Experimental removal of these epigenetic marks at fertilization de-regulates gene expression in the resulting embryos in a paternal chromatin-dependent manner. This demonstrates that epigenetic instructions delivered by the sperm at fertilization are required for correct regulation of gene expression in the future embryos. The epigenetic mechanisms of developmental programming revealed here are likely to relate to the mechanisms involved in transgenerational transmission of acquired traits. Understanding how parental experience can influence development of the progeny has broad potential for improving human health.

Nuclear reprogramming of sperm and somatic nuclei in eggs and oocytes

Eggs and oocytes have a prominent ability to reprogram sperm nuclei for ensuring embryonic development. The reprogramming activity that eggs/oocytes intrinsically have towards sperm is utilised to reprogram somatic nuclei injected into eggs/oocytes in nuclear transfer (NT) embryos. NT embryos of various species can give rise to cloned animals, demonstrating that eggs/oocytes can confer totipotency even to somatic nuclei. However, many studies indicate that reprogramming of somatic nuclei is not as efficient as that of sperm nuclei. In this review, we explain how and why sperm and somatic nuclei are differentially reprogrammed in eggs/oocytes. Recent studies have shown that sperm chromatin is epigenetically modified to be adequate for early embryonic development, while somatic nuclei do not have such modifications. Moreover, epigenetic memories encoded in sperm chromatin are transgenerationally inherited, implying unique roles of sperm. We also discuss whether somatic nuclei can be artificially modified to acquire sperm-like chromatin states in order to increase the efficiency of nuclear reprogramming.

Histone H3 lysine 9 trimethylation is required for suppressing the expression of an embryonically activated retrotransposon in Xenopus laevis

Transposable elements in the genome are generally silenced in differentiated somatic cells. However, increasing evidence indicates that some of them are actively transcribed in early embryos and the proper regulation of retrotransposon expression is essential for normal development. Although their developmentally regulated expression has been shown, the mechanisms controlling retrotransposon expression in early embryos are still not well understood. Here, we observe a dynamic expression pattern of retrotransposons with three out of ten examined retrotransposons (1a11, λ-olt 2-1 and xretpos(L)) being transcribed solely during early embryonic development. We also identified a transcript that contains the long terminal repeat (LTR) of λ-olt 2-1 and shows a similar expression pattern to λ-olt 2-1 in early Xenopus embryos. All three retrotransposons are transcribed by RNA polymerase II. Although their expression levels decline during development, the LTRs are marked by histone H3 lysine 4 trimethylation. Furthermore, retrotransposons, especially λ-olt 2-1, are enriched with histone H3 lysine 9 trimethylation (H3K9me3) when their expression is repressed. Overexpression of lysine-specific demethylase 4d removes H3K9me3 marks from Xenopus embryos and inhibits the repression of λ-olt 2-1 after gastrulation. Thus, our study shows that H3K9me3 is important for silencing the developmentally regulated retrotransposon in Xenopus laevis.

Creating a Community of Data Champions

Research Data Management (RDM) presents an unusual challenge for service providers in Higher Education. There is increased awareness of the need for training in this area but the nature of the discipline-specific practices involved make it difficult to provide training across a multi-disciplinary organisation. Whilst most UK universities now have a research data team of some description, they are often small and rarely have the resources necessary to provide targeted training to the different disciplines and research career stages that they are increasingly expected to support. This practice paper describes the approach taken at the University of Cambridge to address this problem by creating a community of Data Champions. This collaborative initiative, working with researchers to provide training and advocacy for good RDM practice, allows for more discipline-specific training to be given, researchers to be credited for their expertise and creates an opportunity for those interested in RDM to exchange knowledge with others. The ‘community of practice’ model has been used in many sectors, including Higher Education, to facilitate collaboration across organisational units and this initiative will adopt some of the same principles to improve communication across a decentralised institution. The Data Champions initiative at Cambridge was launched in September 2016 and this paper reports on the early months, plans for building the community in the future and the possible risks associated with this approach to providing RDM services.

Could Open Research benefit Cambridge University researchers

This is a write-up of the discussions had during the “Improving the research process: discussing an ‘open research’ policy” event held by the Office of Scholarly Communication on the 8th of June 2016. A corrected version of this write-up was added to this record on the 3rd of August 2016. A correction has been made to Alasdair Russells affiliation.

Sperm and spermatids contain different proteins and bind distinct egg factors.

Spermatozoa are more efficient at supporting normal embryonic development than spermatids, their immature, immediate precursors. This suggests that the sperm acquires the ability to support embryonic development during spermiogenesis (spermatid to sperm maturation). Here, using Xenopus laevis as a model organism, we performed 2-D Fluorescence Difference Gel Electrophoresis (2D-DIGE) and mass spectrometry analysis of differentially expressed proteins between sperm and spermatids in order to identify factors that could be responsible for the efficiency of the sperm to support embryonic development. Furthermore, benefiting from the availability of egg extracts in Xenopus, we also tested whether the chromatin of sperm could attract different egg factors compared to the chromatin of spermatids. Our analysis identified: (1) several proteins which were present exclusively in sperm; but not in spermatid nuclei and (2) numerous egg proteins binding to the sperm (but not to the spermatid chromatin) after incubation in egg extracts. Amongst these factors we identified many chromatin-associated proteins and transcriptional repressors. Presence of transcriptional repressors binding specifically to sperm chromatin could suggest its preparation for the early embryonic cell cycles, during which no transcription is observed and suggests that sperm chromatin has a unique protein composition, which facilitates the recruitment of egg chromatin remodelling factors. It is therefore likely that the acquisition of these sperm-specific factors during spermiogenesis makes the sperm chromatin suitable to interact with the maternal factors and, as a consequence, to support efficient embryonic development.