Generations affected by histone changes: Parent and even grandparent environmental exposure can transmit adverse health effects to offspring. The mechanism of transmission is unclear, but some studies have implicated variations in DNA methylation. In a mouse model, Siklenka et al. found that alterations in histone methylation during sperm formation in one generation leads to reduced survival and developmental abnormalities in three subsequent generations (see the Perspective by McCarrey). Although changes in DNA methylation were not observed, altered sperm RNA content and abnormal gene expression in offspring were measured. Thus, chromatin may act as a mediator of molecular memory in transgenerational inheritance. Science , this issue p. 10.1126/science.aab2006 ; see also p. 634

In mammals, the study of gene expression in the preimplantation embryo has been difficult because the standard procedures used to quantify mRNA gener

Maternal-zygotic transition (MZT) is a complex phenomenon characterized by the initiation of transcription in the embryo and the replacement of maternal mRNA with embryonic mRNA. In order for this to occur, transcriptional activation requires various factors and conditions. Our hypothesis is that the lack of transcription in the bovine pre-MZT embryo is due, in part, to an incomplete or dormant transcriptional apparatus. Therefore, in accordance with this hypothesis, functioning transcriptional mechanisms should appear in the eight-cell bovine embryo to facilitate embryonic transcription during the MZT. With this in mind, we examined the presence of selected transcription factors during preimplantation embryo development to establish how their transcript levels change in bovine pre-MZT embryos. To achieve this goal, real-time reverse transcription-polymerase chain reaction was used to quantify the mRNA level of several different transcription factors (YY1, HMGA1, RY-1, P300, CREB, YAP65, HMGN1, HMGB1, NFAR, OCT-4, TEAD2, ATF-1, HMGN2, MSY2, and TBP) in germinal vesicle (GV) and metaphase II (MII) bovine oocytes and in two-, four-, eight-cell, and blastocyst stage embryos produced in vitro. Our results demonstrate that all genes examined can be grouped into five different categories according to their mRNA expression patterns at the developmental stages observed. To summarize, all transcription factors studied were present in pre-MZT embryos and the expression pattern of many of them suggest a potential role in MZT.

The first crucial step in the developmental program occurs during pre-implantation, the time after the oocyte has been fertilized and before the embryo implants in the uterus. This period represents a vulnerable window as the epigenome undergoes dynamic changes in DNA methylation profiles. Alterations in the early embryonic reprogramming wave can impair DNA methylation patterns and induce permanent changes to the developmental program, leading to the onset of adverse health outcomes in offspring. Although there is an increasing body of evidence indicating that harmful exposures during pre-implantation embryo development can trigger lasting epigenetic alterations in offspring, the mechanisms are still not fully understood. Since physiological or pathological changes in DNA methylation can occur as a response to environmental cues, proper environmental milieu plays a critical role in the success of embryonic development. In this review, we depict the mechanisms behind the embryonic epigenetic reprogramming of DNA methylation and highlight how maternal environmental stressors (e.g., alcohol, heat stress, nutrient availability) during pre-implantation and assisted reproductive technology procedures affect development and DNA methylation marks.

Significance: Our study shows that the clotting protein tissue factor (TF) controls the state of tumor dormancy and does so in conjunction with recruitment of inflammatory cells and blood vessels. We show that indolent glioma cells remain harmless in mice unless rendered TF positive. Our work also demonstrates the ability of TF to indirectly influence the DNA of cancer cells by facilitating gene mutations and silencing. This ability is important because injury, cardiovascular disease, or other conditions may activate the clotting system and contribute to the awakening of occult cancer cells. This understanding also may suggest a prophylactic use of blood thinners in cases where dormant cancer cells and clotting are suspected to coexist (e.g., after surgery).

Mammalian oocytes are very unique cells with an unlimited developmental potential. These totipotent cells are able to remove existing gene-expression patterns and to impose new ones. However, genome reprogramming is still a mystery. Posttranslational modifications by acetylation of the N-termini portion of histones composing the nucleosome are involved in genome reprogramming. These modifications alter the higher-order chromatin structure to render the DNA accessible to the regulatory and transcriptional machinery. In the present study, we have investigated, to our knowledge for the first time, precise expression patterns of seven genes involved in chromatin structure throughout bovine embryo development. Oocytes harvested from bovine ovaries were used for in vitro production of germinal vesicle oocytes, metaphase II oocytes, 2- and 8-cell embryos, and blastocysts. Total RNA was extracted from pools (triplicates) of 20 oocytes or from embryos of each developmental stage. By means of quantitative reverse transcription-polymerase chain reaction using SYBR Green to detect double-stranded DNA, mRNA expression profiles for histone deacetylases (HDAC1, HDAC2, HDAC3, and HDAC7), histone acetyltransferases (GCN5 and HAT1), and histone H2A were established. Transcripts for all genes were detected at all stages from the oocyte to the blastocyst. The HDAC1, HDAC2 (class I HDAC), and HAT1 (type B HAT) revealed similar expression profiles. The HDAC3 (class I HDAC) tends to have an expression profile similar to those of HDAC1, HDAC2, and HAT1, whereas the HDAC7 (class II HDAC) and GCN5 (type A HAT) profiles were different from those three. These results indicate variable levels of histone deacetylases and histone acetyltransferases throughout embryonic development and may indicate the ones that are involved in somatic remodeling.