Chromatin Flavors: Chromatin composition and domain organization in Drosophila melanogaster

Chromatin was originally identified by W. Flemming in 1882 as not much more than the stainable substance of the cell nucleus. Flemming named this substance according to the Greek word “chroma”, meaning color. In 1911 chromatin was characterized as proteins, named histones, that were attached to nucleic acid (DNA). In the following years it became clear that chromatin formed the structural basis of genetic information. Not until more than 30 years later the DNA, and not the histone proteins as was widely expected, was identified as the carrier of the genetic information. In 1952 the role of DNA in inheritance was confirmed and not much later Watson and Crick discovered the double-helical structure of DNA based on the DNA crystal analyses of Franklin, Gosling and Wilkins

A Conserved Noncoding Locus Regulates Random Monoallelic Xist Expression across a Topological Boundary

cis-Regulatory communication is crucial in mammalian development and is thought to be restricted by the spatial partitioning of the genome in topologically associating domains (TADs). Here, we discovered that the Xist locus is regulated by sequences in the neighboring TAD. In particular, the promoter of the noncoding RNA Linx (LinxP) acts as a long-range silencer and influences the choice of X chromosome to be inactivated. This is independent of Linx transcription and independent of any effect on Tsix, the antisense regulator of Xist that shares the same TAD as Linx. Unlike Tsix, LinxP is well conserved across mammals, suggesting an ancestral mechanism for random monoallelic Xist regulation. When introduced in the same TAD as Xist, LinxP switches from a silencer to an enhancer. Our study uncovers an unsuspected regulatory axis for X chromosome inactivation and a class of cis-regulatory effects that may exploit TAD partitioning to modulate developmental decisions.Galupa et al. uncover elements important for Xist regulation in its neighboring TAD and reveal that these elements can influence gene regulation both within and between topological domains. These findings, in a context where dynamic, developmental expression is necessary, challenge current models for TAD-based gene-regulatory landscapes

Cis- and trans-regulation in X inactivation

Female mammalian cells compensate dosage of X-linked gene expression through the inactivation of one of their two X chromosomes. X chromosome inactivation (XCI) in eutherians is dependent on the non-coding RNA Xist that is up-regulated from the future inactive X chromosome, coating it and recruiting factors involved in silencing and altering its chromatin state. Xist lies within the X-inactivation center (Xic), a region on the X that is required for XCI, and is regulated in cis by elements on the X chromosome and in trans by diffusible factors. In this review, we summarize the latest results in cis- and trans-regulation of the Xic. We discuss how the organization of the Xic in topologically associating domains is important for XCI (cis-regulation) and how proteins in the pluripotent state and upon development or differentiation of embryonic stem cells control proper inactivation of one X chromosome (trans-regulation)