Long Noncoding RNAs: The past 5 years have uncovered thousands of long (>100 nucleotides) noncoding RNAs (lncRNAs) outpacing our understanding of their functions and mechanisms in regulating the genome. Lee (p. 1435 ) reviews the known and suspected means by which these intriguing molecules control gene expression locally and at great distances, considers potential universal roles for lncRNAs, and warns that classifying these intriguing molecules may be quite challenging given their diversity. The very long noncoding RNA, Airn , silences the Igf2r (insulin-like growth factor 2 receptor) imprinted gene cluster in mammals. Latos et al. (p. 1469 ) show in mouse cells that, rather than recruiting enzymes that modify histones to repress the locus, it is the act of transcription of Airn (and not the Airn gene product) that results in the silencing.

To determine the dynamics of allelic-specific expression during mouse development, we analyzed RNA-seq data from 23 F1 tissues from different developmental stages, including 19 female tissues allowing X chromosome inactivation (XCI) escapers to also be detected. We demonstrate that allelic expression arising from genetic or epigenetic differences is highly tissue-specific. We find that tissue-specific strain-biased gene expression may be regulated by tissue-specific enhancers or by post-transcriptional differences in stability between the alleles. We also find that escape from X-inactivation is tissue-specific, with leg muscle showing an unexpectedly high rate of XCI escapers. By surveying a range of tissues during development, and performing extensive validation, we are able to provide a high confidence list of mouse imprinted genes including 18 novel genes. This shows that cluster size varies dynamically during development and can be substantially larger than previously thought, with the Igf2r cluster extending over 10 Mb in placenta.

P450‐aromatase is the terminal estrogen‐synthesizing enzyme and a key gene in avian sex determination. Aromatase is expressed specifically in female gonads, but not male gonads, at the onset of sexual differentiation. This enzyme shows temporal and spatial colocalization with the forkhead transcription factor FOXL2 in the embryonic chicken ovary, suggesting a causal link. Mutations in FOXL2 are associated with premature ovarian failure in humans. Foxl2 null mice also present with premature ovarian failure. Here, we show that FOXL2 expression is reduced but not abolished in chicken embryos subjected to experimental female to male sex‐reversal with an aromatase inhibitor. This finding suggests that FOXL2 lies upstream of aromatase in avian sex determination, but that it responds to depleted estrogen synthesis. The reduction in FOXL2 expression may be accounted for by interruption of a positive feedback loop by means of estrogen, or the influence of testis promoting factors such as SOX9 and DMRT1 in the masculinized gonads. Developmental Dynamics 233:1052–1055, 2005.

Sex is determined genetically in all birds, but the underlying mechanism remains unknown. All species have a ZZ/ZW sex chromosome system characterised by female (ZW) heterogamety, but the chromosomes themselves can be heteromorphic (in most birds) or homomorphic (in the flightless ratites). Sex in birds might be determined by the dosage of a Z-linked gene (two in males, one in females) or by a dominant ovary-determining gene carried on the W sex chromosome, or both. Sex chromosome aneuploidy has not been conclusively documented in birds to differentiate between these possibilities. By definition, the sex chromosomes of birds must carry one or more sex-determining genes. In this review of avian sex determination, we ask what, when and where? What is the nature of the avian sex determinant? When should it be expressed in the developing embryo, and where is it expressed? The last two questions arise due to evidence suggesting that sex-determining genes in birds might be operating prior to overt sexual differentiation of the gonads into testes or ovaries, and in tissues other than the urogenital system.

Non-coding (nc) RNA silencing of imprinted genes in extra-embryonic tissues provides a good model for understanding an underexamined aspect of gene regulation by macro or long ncRNAs, that is their action as long-range cis-silencers. Numerous long intergenic ncRNAs (lincRNAs) have been recently discovered that are thought to regulate gene expression, some of which have been associated with disease. The few shown to regulate protein-coding genes are suggested to act by targeting repressive or active chromatin marks. Correlative evidence also indicates that imprinted macro ncRNAs cause long-range cis-silencing in placenta by targeting repressive histone modifications to imprinted promoters. It is timely, however, to consider alternative explanations consistent with the published data, whereby transcription alone could cause gene silencing at a distance.

Imprinted genes in mice and humans mainly occur in clusters that are associated with differential DNA methylation of an imprint control element (ICE) and at least one nonprotein-coding RNA (ncRNA). Imprinted gene silencing is achieved by parental-specific insulator activity of the unmethylated ICE mediated by CTCF (CCCTC-binding factor) binding, or by ncRNA expression from a promoter in the unmethylated ICE. In many imprinted clusters, some genes, particularly those located furthest away from the ICE, show imprinted expression only in extraembryonic tissues. Recent research indicates that genes showing imprinted expression only in extraembryonic tissues may be regulated by different epigenetic mechanisms compared with genes showing imprinted expression in extraembryonic tissues and in embryonic/adult tissues. The study of extraembryonic imprinted expression, thus, has the potential to illuminate novel epigenetic strategies, but is complicated by the need to collect tissue from early stages of mouse development, when extraembryonic tissues may be contaminated by maternal cells or be present in limited amounts. Research in this area would be advanced by the development of an in vitro model system in which genetic experiments could be conducted in less time and at a lower cost than with mouse models. Here, we summarize what is known about the mechanisms regulating imprinted expression in mouse extraembryonic tissues and explore the possibilities for developing an in vitro model.