Coordinated Expression Domains in Mammalian Genomes

Gene order in eukaryotic genomes is not random. Genes showing similar expression (coexpression) patterns are often clustered along the genome. The goal of this study is to characterize coexpression clustering in mammalian genomes and to investigate the underlying mechanisms.We detect clustering of coexpressed genes across multiple scales, from neighboring genes to chromosomal domains that span tens of megabases and, in some cases, entire chromosomes. Coexpression domains may be positively or negatively correlated with other domains, within and between chromosomes. We find that long-range expression domains are associated with gene density, which in turn is related to physical organization of the chromosomes within the nucleus. We show that gene expression changes between healthy and diseased tissue samples occur in a gene density-dependent manner.We demonstrate that coexpression domains exist across multiple scales. We identify potential mechanisms for short-range as well as long-range coexpression domains. We provide evidence that the three-dimensional architecture of the chromosomes may underlie long-range coexpression domains. Chromosome territory reorganization may play a role in common human diseases such as Alzheimer's disease and psoriasis

Tissue-specific gene repositioning by muscle nuclear membrane proteins enhances repression of critical developmental genes during myogenesis

Whether gene repositioning to the nuclear periphery during differentiation adds another layer of regulation to gene expression remains controversial. Here, we resolve this by manipulating gene positions through targeting the nuclear envelope transmembrane proteins (NETs) that direct their normal repositioning during myogenesis. Combining transcriptomics with high-resolution DamID mapping of nuclear envelope-genome contacts, we show that three muscle-specific NETs, NET39, Tmem38A, and WFS1, direct specific myogenic genes to the nuclear periphery to facilitate their repression. Retargeting a NET39 fragment to nucleoli correspondingly repositioned a target gene, indicating a direct tethering mechanism. Being able to manipulate gene position independently of other changes in differentiation revealed that repositioning contributes ⅓ to ⅔ of a gene’s normal repression in myogenesis. Together, these NETs affect 37% of all genes changing expression during myogenesis, and their combined knockdown almost completely blocks myotube formation. This unequivocally demonstrates that NET-directed gene repositioning is critical for developmental gene regulation

NEW ALTERNATIVE TO THE DUNHAM POTENTIAL FOR DIATOMIC MOLECULES

Present address of Gary Simons: Department of Chemistry, Wichita State University, Wichita, Kansas, 67208.Author Institution: Department of Chemistry, The Johns Hopkins UniversityA new systematic procedure for constructing potential curves for diatomic molecules is developed. The procedure is similar to the wellknown Dunham method, except that the expansion parameter is ($R - R_{e})/R$ instead of $(R - R_{e})/Re$. The new expansion, which has a formal theoretical basis, is shown to be superior in terms of both rate of convergence and region of convergence. The proper behavior of the potential at large R is shown to allow one to calculate dissociation energies directly from the Dunham coefficients. Several diatomics are explicitly treated, and possible extensions and applications to polyatomic molecules are discussed