Regulatory links between imprinted genes: evolutionary predictions and consequences

Genomic imprinting is essential for development and growth and plays diverse roles in physiology and behaviour. Imprinted genes have traditionally been studied in isolation or in clusters with respect to cis-acting modes of gene regulation, both from a mechanistic and evolutionary point of view. Recent studies in mammals, however, reveal that imprinted genes are often co-regulated and are part of a gene network involved in the control of cellular proliferation and differentiation. Moreover, a subset of imprinted genes acts in trans on the expression of other imprinted genes. Numerous studies have modulated levels of imprinted gene expression to explore phenotypic and gene regulatory consequences. Increasingly, the applied genome-wide approaches highlight how perturbation of one imprinted gene may affect other maternally or paternally expressed genes. Here, we discuss these novel findings and consider evolutionary theories that offer a rationale for such intricate interactions among imprinted genes. An evolutionary view of these trans-regulatory effects provides a novel interpretation of the logic of gene networks within species and has implications for the origin of reproductive isolation between species.     

Gene expression changes accompanying p53 activity during estrogen treatment of osteoblasts

Estrogen is known to be anabolic for bone and we have used estrogen treatment as a paradigm to understand how p53 may affect osteoblast differentiation. In previous studies we have shown estrogen treatment to increase p53 functional activity in osteoblasts. Estrogen has been suggested to inhibit apoptosis in osteoblasts. Since the significance of a p53 increase during estrogen treatment is not apparent, we investigated the environment within osteoblasts after treatment with estrogen. We observed two peaks of p53 activity during continuous treatment of 17-[beta]-estradiol (E2) for 72h. The gene expression profile of different cell cycle regulators and apoptosis related genes at different times during treatment with 17-[beta]-estradiol were tested using gene arrays. There was an early increase in expression of several genes involved in apoptosis. This was followed by changes in expression of several genes involved in cell survival and stress response. The second peak of activity was associated with increase in expression of cell cycle regulators. Our results suggest that p53 activity may be a result of activation of several signaling pathways involving apoptosis, cell survival and cell cycle arrest. P53 may have a role in integrating these responses, which eventually results in cell cycle arrest and expression of differentiation markers.     

Recent advances in the genetic investigation of osteoarthritis

Osteoarthritis (OA) demonstrates considerable clinical heterogeneity, generating heated debate over whether OA is a single disease or a complex mix of disparate diseases and concerning which tissues are principally involved in disease initiation and progression. Epidemiological studies have demonstrated a major genetic component to OA risk. However, these studies have also revealed differences in risk between males and females and for disease at different skeletal sites. This observation has resulted in the concept of genes for specific sites rather than a generalised OA phenotype. Recent breakthroughs have shed considerable light on the nature of OA genetic susceptibility. Many candidate genes have been confirmed, such as the interleukin-1 gene cluster and the oestrogen alpha-receptor gene ESR1. Genome-wide linkage scans have revealed several regions harbouring novel loci, some of which are beginning to yield their genes.     

Reference genes for measuring mRNA expression

The aim of this review is to find answers to some of the questions surrounding reference genes and their reliability for quantitative experiments. Reference genes are assumed to be at a constant expression level, over a range of conditions such as temperature. These genes, such as GADPH and beta-actin, are used extensively for gene expression studies using techniques like quantitative PCR. There have been several studies carried out on identifying reference genes. However, a lot of evidence indicates issues to the general suitability of these genes. Recent studies had shown that different factors, including the environment and methods, play an important role in changing the expression levels of the reference genes. Thus, we conclude that there is no reference gene that can deemed suitable for all the experimental conditions. In addition, we believe that every experiment will require the scientific evaluation and selection of the best candidate gene for use as a reference gene to obtain reliable scientific results.     

Analysis of molecular markers in three different tomato cultivars exposed to ozone stress

Three differentially expressed cDNAs have been isolated from ozone treated tomato seedlings. Their level of expression after ozone exposure has been analysed in three tomato cultivars with different sensitivity to ozone (Nikita, Alisa Craig and Valenciano). These comparative analyses have been extended to a number of genes involved in antioxidative, wounding or pathogenesis responses, showing several differences among cultivars that could be related with their different sensitivity to ozone. Gene response to ozone was affected not only by the period and dose of ozone exposure (short time or chronic), but also by growth conditions (controlled growth chamber or field). Comparison of gene expression patterns puts on evidence the needing of validation in field of experiments performed with plants grown under controlled conditions. Our results suggest that changes in genes expression, observed after ozone treatment in field, are affected by additional factors related to environmental clues.     

Nuclear phosphoinositide regulation of chromatin

Phospholipid signaling has clear connections to a wide array of cellular processes, particularly in gene expression and in controlling the chromatin biology of cells. However, most of the work elucidating how phospholipid signaling pathways contribute to cellular physiology have studied cytoplasmic membranes, while relatively little attention has been paid to the role of phospholipid signaling in the nucleus. Recent work from several labs has shown that nuclear phospholipid signaling can have important roles that are specific to this cellular compartment. This review focuses on the nuclear phospholipid functions and the activities of phospholipid signaling enzymes that regulate metazoan chromatin and gene expression. In particular, we highlight the roles that nuclear phosphoinositides play in several nuclear‐driven physiological processes, such as differentiation, proliferation, and gene expression. Taken together, the recent discovery of several specifically nuclear phospholipid functions could have dramatic impact on our understanding of the fundamental mechanisms that enable tight control of cellular physiology.