Locus-specific targeting to the X chromosome revealed by the RNA interactome of CTCF.

CTCF is a master regulator that plays important roles in genome architecture and gene expression. How CTCF is recruited in a locus-specific manner is not fully understood. Evidence from epigenetic processes, such as X chromosome inactivation (XCI), indicates that CTCF associates functionally with RNA. Using genome-wide approaches to investigate the relationship between its RNA interactome and epigenomic landscape, here we report that CTCF binds thousands of transcripts in mouse embryonic stem cells, many in close proximity to CTCF's genomic binding sites. CTCF is a specific and high-affinity RNA-binding protein (Kd < 1 nM). During XCI, CTCF differentially binds the active and inactive X chromosomes and interacts directly with Tsix, Xite, and Xist RNAs. Tsix and Xite RNAs target CTCF to the X inactivation center, thereby inducing homologous X chromosome pairing. Our work elucidates one mechanism by which CTCF is recruited in a locus-specific manner and implicates CTCF-RNA interactions in long-range chromosomal interactions.

Genome-wide identification of polycomb-associated RNAs by RIP-seq.

Polycomb proteins play essential roles in stem cell renewal and human disease. Recent studies of HOX genes and X inactivation have provided evidence for RNA cofactors in Polycomb repressive complex 2 (PRC2). Here we develop a RIP-seq method to capture the PRC2 transcriptome and identify a genome-wide pool of >9000 PRC2-interacting RNAs in embryonic stem cells. The transcriptome includes antisense, intergenic, and promoter-associated transcripts, as well as many unannotated RNAs. A large number of transcripts occur within imprinted regions, oncogene and tumor suppressor loci, and stem cell-related bivalent domains. We provide evidence for direct RNA-protein interactions, most likely via the Ezh2 subunit. We also identify Gtl2 RNA as a PRC2 cofactor that directs PRC2 to the reciprocally imprinted Dlk1 coding gene. Thus, Polycomb proteins interact with a genome-wide family of RNAs, some of which may be used as biomarkers and therapeutic targets for human disease.

Getting a head start: the importance of personal genetics education in high schools.

With advances in sequencing technology, widespread and affordable genome sequencing will soon be a reality. However, studies suggest that "genetic literacy" of the general public is inadequate to prepare our society for this unprecedented access to our genetic information. As the current generation of high school students will come of age in an era when personal genetic information is increasingly utilized in health care, it is of vital importance to ensure these students understand the genetic concepts necessary to make informed medical decisions. These concepts include not only basic scientific knowledge, but also considerations of the ethical, legal, and social issues that will arise in the age of personal genomics. In this article, we review the current state of genetics education, highlight issues that we believe need to be addressed in a comprehensive genetics education curriculum, and describe our education efforts at the Harvard Medical School-based Personal Genetics Education Project.

RNA in the loop.

Long noncoding RNAs (lncRNAs) have been implicated in a variety of biological roles, particularly as cis or trans gene expression regulators. Reporting recently in Nature, Lai et al. (2013) show that a class of gene-activating lncRNAs combines two gene regulation paradigms: enhancer-directed chromosomal looping and RNA-mediated protein effector recruitment.

Long noncoding RNAs: past, present, and future.

Long noncoding RNAs (lncRNAs) have gained widespread attention in recent years as a potentially new and crucial layer of biological regulation. lncRNAs of all kinds have been implicated in a range of developmental processes and diseases, but knowledge of the mechanisms by which they act is still surprisingly limited, and claims that almost the entirety of the mammalian genome is transcribed into functional noncoding transcripts remain controversial. At the same time, a small number of well-studied lncRNAs have given us important clues about the biology of these molecules, and a few key functional and mechanistic themes have begun to emerge, although the robustness of these models and classification schemes remains to be seen. Here, we review the current state of knowledge of the lncRNA field, discussing what is known about the genomic contexts, biological functions, and mechanisms of action of lncRNAs. We also reflect on how the recent interest in lncRNAs is deeply rooted in biology's longstanding concern with the evolution and function of genomes.