Simultaneous disruption of PRC2 and enhancer function underlies histone H3.3-K27M oncogenic activity in human hindbrain neural stem cells.

Driver mutations in genes encoding histone H3 proteins resulting in p.Lys27Met substitutions (H3-K27M) are frequent in pediatric midline brain tumors. However, the precise mechanisms by which H3-K27M causes tumor initiation remain unclear.

PRC2.1 and PRC2.2 Synergize to Coordinate H3K27 Trimethylation.

Polycomb repressive complex 2 (PRC2) is composed of EED, SUZ12, and EZH1/2 and mediates mono-, di-, and trimethylation of histone H3 at lysine 27. At least two independent subcomplexes exist, defined by their specific accessory proteins: PRC2.1 (PCL1-3, EPOP, and PALI1/2) and PRC2.

Circadian clock protein BMAL1 regulates IL-1β in macrophages via NRF2.

A variety of innate immune responses and functions are dependent on time of day, and many inflammatory conditions are associated with dysfunctional molecular clocks within immune cells. However, the functional importance of these innate immune clocks has yet to be fully characterized. NRF2 plays a critical role in the innate immune system, limiting inflammation via reactive oxygen species (ROS) suppression and direct repression of the proinflammatory cytokines, IL-1β and IL-6.

A Family of Vertebrate-Specific Polycombs Encoded by the LCOR/LCORL Genes Balance PRC2 Subtype Activities.

The polycomb repressive complex 2 (PRC2) consists of core subunits SUZ12, EED, RBBP4/7, and EZH1/2 and is responsible for mono-, di-, and tri-methylation of lysine 27 on histone H3. Whereas two distinct forms exist, PRC2.1 (containing one polycomb-like protein) and PRC2.

The H3K36me2 Methyltransferase Nsd1 Demarcates PRC2-Mediated H3K27me2 and H3K27me3 Domains in Embryonic Stem Cells.

The Polycomb repressor complex 2 (PRC2) is composed of the core subunits Ezh1/2, Suz12, and Eed, and it mediates all di- and tri-methylation of histone H3 at lysine 27 in higher eukaryotes. However, little is known about how the catalytic activity of PRC2 is regulated to demarcate H3K27me2 and H3K27me3 domains across the genome. To address this, we mapped the endogenous interactomes of Ezh2 and Suz12 in embryonic stem cells (ESCs), and we combined this with a functional screen for H3K27 methylation marks.

The TOR-Activating GTPases Gtr1 and Rhb1 Coregulate Starvation Responses and Biofilm Formation.

Target of rapamycin complex 1 (TORC1) is an essential regulator of metabolism in eukaryotic cells and in the fungal pathogen regulates morphogenesis and nitrogen acquisition. Gtr1 encodes a highly conserved GTPase that in regulates nitrogen sensing and TORC1 activation. Here, we characterize the role of in TORC1 activation and compare it with the previously characterized GTPase Rhb1.

Fam60a defines a variant Sin3a-Hdac complex in embryonic stem cells required for self-renewal.

Sin3a is the central scaffold protein of the prototypical Hdac1/2 chromatin repressor complex, crucially required during early embryonic development for the growth of pluripotent cells of the inner cell mass. Here, we compare the composition of the Sin3a-Hdac complex between pluripotent embryonic stem (ES) and differentiated cells by establishing a method that couples two independent endogenous immunoprecipitations with quantitative mass spectrometry. We define the precise composition of the Sin3a complex in multiple cell types and identify the Fam60a subunit as a key defining feature of a variant Sin3a complex present in ES cells, which also contains Ogt and Tet1.

Distinct histone methylation and transcription profiles are established during the development of cellular quiescence in yeast.

Background: Quiescent cells have a low level of gene activity compared to growing cells. Using a yeast model for cellular quiescence, we defined the genome-wide profiles of three species of histone methylation associated with active transcription between growing and quiescent cells, and correlated these profiles with the presence of RNA polymerase II and transcripts.

Results: Quiescent cells retained histone methylations normally associated with transcriptionally active chromatin and had many transcripts in common with growing cells.

Discovering anti-platelet drug combinations with an integrated model of activator-inhibitor relationships, activator-activator synergies and inhibitor-inhibitor synergies.

Identifying effective therapeutic drug combinations that modulate complex signaling pathways in platelets is central to the advancement of effective anti-thrombotic therapies. However, there is no systems model of the platelet that predicts responses to different inhibitor combinations. We developed an approach which goes beyond current inhibitor-inhibitor combination screening to efficiently consider other signaling aspects that may give insights into the behaviour of the platelet as a system.

Genome-wide epistatic expression quantitative trait loci discovery in four human tissues reveals the importance of local chromosomal interactions governing gene expression.

Background: Epistasis (synergistic interaction) among SNPs governing gene expression is likely to arise within transcriptional networks. However, the power to detect it is limited by the large number of combinations to be tested and the modest sample sizes of most datasets. By limiting the interaction search space firstly to cis-trans and then cis-cis SNP pairs where both SNPs had an independent effect on the expression of the most variable transcripts in the liver and brain, we greatly reduced the size of the search space.

HGDP and HapMap analysis by Ancestry Mapper reveals local and global population relationships.

Knowledge of human origins, migrations, and expansions is greatly enhanced by the availability of large datasets of genetic information from different populations and by the development of bioinformatic tools used to analyze the data. We present Ancestry Mapper, which we believe improves on existing methods, for the assignment of genetic ancestry to an individual and to study the relationships between local and global populations. The principle function of the method, named Ancestry Mapper, is to give each individual analyzed a genetic identifier, made up of just 51 genetic coordinates, that corresponds to its relationship to the HGDP reference population.