Inhibition of DNA synthesis does not influence the H1 histone synthesis in Tetrahymena pyriformis

In the protozoan Tetrahymena pyriformis the DNA synthesis is stopped immediately and completely after addition of one of the two DNA synthesis inhibitors methotrexate + uridine and hydroxyurea to a cell suspension. However, the present experiments show, that the accumulation of labeled H1 histone in the inhibited cells is almost totally unaffected for more than two-thirds of a cell cycle after addition of either inhibitor.     

Analysis of a histone H2A variant from fission yeast: evidence for a role in chromosome stability

We have isolated and characterised the pht1 gene from the fission yeast Schizosaccharomyces pombe. The sequence of the predicted translation product has revealed a striking similarity to the family of H2A.F/Z histone variant proteins, which have been found in a variety of different organisms. Cells deleted for the pht1 gene locus grow slowly, exhibit an altered colony morphology, increased resistance to heat shock and show a significant decrease in the fidelity of segregation of an S. pombe minichromosome. We propose that the histone H2A variant encoded by the pht1 gene is important for chromosomal structure and function, possibly including a role in controlling the fidelity of chromosomal segregation during mitosis.     

A comparison of the DNA binding properties of histone-like proteins derived from representatives of the two kingdoms of the Archaea

Abstract The nucleoid protein composition, the enhancement of DNA electrophoretic mobility, the toroidal wrapping and the helical period of DNA complexed with nucleoid proteins from species within the archaeal kingdom Euryarchaeota was shown to contrast with the composition and properties of nucleoid proteins from Sulfolobus solfataricus , a member of the archaeal kingdom Crenarchaeota. This result was seen to support the hypothesis that archaeal histones with homology to the eukaryal hi stone consensus are a diagnostic feature of the Euryarchaeota.     

Improved methods for targeting epigenetic reader domains of acetylated and methylated lysine

Responsible for interpreting histone post-translational modifications, epigenetic reader proteins have emerged as novel therapeutic targets for a wide range of diseases. Chemical probes have been critical in enabling target validation studies and have led to translational advances in cancer and inflammation-related pathologies. Here, we present the most recently reported probes of reader proteins that recognize acylated and methylated lysine. We will discuss challenges associated with achieving potent antagonism of reader domains and review ongoing efforts to overcome these hurdles, focusing on targeting strategies including the use of peptidomimetic ligands, allosteric modulators, and protein degraders.     

Protein Phosphatase 2A Enables Expression of Interleukin 17 (IL-17) through Chromatin Remodeling

Protein phosphatase 2A (PP2A) is a heterotrimeric serine/threonine phosphatase involved in essential cellular functions. T cells from patients with systemic lupus erythematosus (SLE) express high levels of the catalytic subunit of PP2A (PP2Ac). A mouse overexpressing PP2Ac in T cells develops glomerulonephritis in an IL-17-dependent manner. Here, using microarray analyses, we demonstrate that increased expression of PP2Ac grants T cells the capacity to produce an array of proinflammatory effector molecules. Because IL-17 is important in the expression of glomerulonephritis, we studied the mechanism through which PP2Ac dysregulation facilitates its production. We report that PP2Ac is involved in the regulation of the Il17 locus by enhancing histone 3 acetylation through a mechanism that involves activation of interferon regulatory factor 4. Increased histone 3 acetylation of the Il17 locus is shared between T cells of PP2Ac transgenic mice and patients with SLE. We propose that, by promoting the inflammatory capacity of T cells, PP2Ac dysregulation contributes to the pathogenesis of SLE.     

Effect of thioacetamide,growth hormone or partial hepatectomy on spermidine acetylase activity of rat liver cytosol

Rat liver cytosol extracts catalyzed the formation of monoacetylspermidine when incubated with acetyl-CoA and spermidine.This activity was enhanced 15-fold by administration of thioacetamide (150 mg/kg). The peak of activity occurred 18–24 h after treatment with the drug and then declined reaching control levels by 76 h. Previous studies have shown that ornithine decarboxylase activity was also greatly increased over this time period. Putrescine content in the liver was increased 80–90-fold at 18–24 h and then declined. Spermidine levels were decreased significantly over the period 12–24 h after thioacetamide treatment and then increased substantially at later times. These results are consistent with the hypothesis that, at early times after administration of thioacetamide, the increase in putrescine content is brought about both by decarboxylation of ornithine and by degradation of monoacetylspermidine.Spermidine acetylase activity was also measured in liver extracts prepared after two other physiological stimuli known to enhance ornithine decarboxylase activity were used. Both growth hormone treatment and partial hepatectomy produced an early 2–3-fold increase in the cytosolic spermidine acetylase activity.     

The histone demethylase Jmjd3 regulates zebrafish myeloid development by promoting spi1 expression

The histone demethylase Jmjd3 plays a critical role in cell lineage specification and differentiation at various stages of development. However, its function during normal myeloid development remains poorly understood. Here, we carried out a systematic in vivo screen of epigenetic factors for their function in hematopoiesis and identified Jmjd3 as a new epigenetic factor that regulates myelopoiesis in zebrafish. We demonstrated that jmjd3 was essential for zebrafish primitive and definitive myelopoiesis, knockdown of jmjd3 suppressed the myeloid commitment and enhanced the erythroid commitment. Only overexpression of spi1 but not the other myeloid regulators rescued the myeloid development in jmjd3 morphants. Furthermore, preliminary mechanistic studies demonstrated that Jmjd3 could directly bind to the spi1 regulatory region to alleviate the repressive H3K27me3 modification and activate spi1 expression. Thus, our studies highlight that Jmjd3 is indispensable for early zebrafish myeloid development by promoting spi1 expression.