When transfusion causes a splitting headache: A case report and rapid review of transfusion-associated reversible cerebral vasoconstriction syndrome.

Reversible cerebral vasoconstriction syndrome (RCVS) is a rare and understudied transfusion reaction most commonly seen in adult females after correction of chronic, severe anemia. Transfusion-associated RCVS (TA-RCVS) typically presents with thunderclap headaches and one or more systemic (hypertension, nausea/vomiting) or neurologic (seizure, stroke, visual changes) symptoms within a week after red blood cell transfusion. Treatment of RCVS is based on blood pressure control; a recent study suggested that early use of nimodipine could shorten the disease course.

A bipartite element with allele-specific functions safeguards DNA methylation imprints at the Dlk1-Dio3 locus.

Loss of imprinting (LOI) results in severe developmental defects, but the mechanisms preventing LOI remain incompletely understood. Here, we dissect the functional components of the imprinting control region of the essential Dlk1-Dio3 locus (called IG-DMR) in pluripotent stem cells. We demonstrate that the IG-DMR consists of two antagonistic elements: a paternally methylated CpG island that prevents recruitment of TET dioxygenases and a maternally unmethylated non-canonical enhancer that ensures expression of the Gtl2 lncRNA by counteracting de novo DNA methyltransferases.

Dynamic 3D Chromatin Reorganization during Establishment and Maintenance of Pluripotency.

Higher-order chromatin structure is tightly linked to gene expression and therefore cell identity. In recent years, the chromatin landscape of pluripotent stem cells has become better characterized, and unique features at various architectural levels have been revealed. However, the mechanisms that govern establishment and maintenance of these topological characteristics and the temporal and functional relationships with transcriptional or epigenetic features are still areas of intense study.

Publisher Correction: TET proteins safeguard bivalent promoters from de novo methylation in human embryonic stem cells.

The version of the Supplementary Text and Figures file initially posted was missing Supplementary Tables 1-6 and the Supplementary Note and used incorrect versions of the supplementary figures.

Author Correction: TET proteins safeguard bivalent promoters from de novo methylation in human embryonic stem cells.

In the version of this article initially published, in the Methods, the Gene Expression Omnibus accession code for H3K36me3 ChIP-seq data was incorrectly given as GSM1003585 instead of GSM733725. The error has been corrected in the HTML, PDF and print versions of the article.

TET proteins safeguard bivalent promoters from de novo methylation in human embryonic stem cells.

TET enzymes oxidize 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), which can lead to DNA demethylation. However, direct connections between TET-mediated DNA demethylation and transcriptional output are difficult to establish owing to challenges in distinguishing global versus locus-specific effects. Here we show that TET1, TET2 and TET3 triple-knockout (TKO) human embryonic stem cells (hESCs) exhibit prominent bivalent promoter hypermethylation without an overall corresponding decrease in gene expression in the undifferentiated state.

Widespread Mitotic Bookmarking by Histone Marks and Transcription Factors in Pluripotent Stem Cells.

During mitosis, transcription is halted and many chromatin features are lost, posing a challenge for the continuity of cell identity, particularly in fast cycling stem cells, which constantly balance self-renewal with differentiation. Here we show that, in pluripotent stem cells, certain histone marks and stem cell regulators remain associated with specific genomic regions of mitotic chromatin, a phenomenon known as mitotic bookmarking. Enhancers of stem cell-related genes are bookmarked by both H3K27ac and the master regulators OCT4, SOX2, and KLF4, while promoters of housekeeping genes retain high levels of mitotic H3K27ac in a cell-type invariant manner.

Nucleation by rRNA Dictates the Precision of Nucleolus Assembly.

Membrane-less organelles are intracellular compartments specialized to carry out specific cellular functions. There is growing evidence supporting the possibility that such organelles form as a new phase, separating from cytoplasm or nucleoplasm. However, a main challenge to such phase separation models is that the initial assembly, or nucleation, of the new phase is typically a highly stochastic process and does not allow for the spatiotemporal precision observed in biological systems.