Search results for "Histone"
showing 10 items of 522 documents
A multifunctional bicupin serves as precursor for a chromosomal protein of Pisum sativum seeds.
2005
The fact that the psp54 gene codes for p16, a seed chromatin protein of Pisum sativum, has been described previously. In the present paper it is shown that p54, the p16 precursor, also exists as a free polypeptide in pea and that it also yields p38, a second polypeptide from the N-terminal region of p54, which is co-localized at a subcellular level with p16. By using antibodies against pea p16 and p38, it was found that these proteins are present in the members of the tribe Viciae examined. Sequence analysis and 3D modelling indicates that p54 proteins belong to the cupin superfamily, and that they are related to sucrose binding proteins and, to a lesser extent, to vicilin-type seed storage…
Structural Characterization of Set1 RNA Recognition Motifs and their Role in Histone H3 Lysine 4 Methylation
2006
Departament de Bioquimica iBiologia Molecular, Universitatde Valencia, C/Dr Moliner 50,46100, Burjassot, SpainThe yeast Set1 histone H3 lysine 4 (H3K4) methyltransferase contains, inaddition to its catalytic SET domain, a conserved RNA recognition motif(RRM1). We present here the crystal structure and the secondary structureassignment in solution of the Set1 RRM1. Although RRM1 has the expectedβαββαβ RRM-fold, it lacks the typical RNA-binding features of thesemodules. RRM1 is not able to bind RNA by itself in vitro, but a constructcombining RRM1 with a newly identified downstream RRM2 specificallybinds RNA. Invivo,H3K4 methylation isnot affectedbyapoint mutation inRRM2 that preserves Set1 s…
Macrocyclic oligoureas with xanthene and diphenyl ether units
2009
Two cyclic oligoureas with 64- and 80-membered rings in which two sets of three or four rigid xanthene (X) units are connected via flexible diphenyl ether (D) units were synthesized by a stepwise fragment condensation. The compounds were characterized by (1)H NMR and ESI mass spectrometry. The structure of the cyclic octamer (XXXDXXXD) was additionally confirmed by single crystal X-ray analysis. The molecule assumes a strongly folded conformation with distorted C(2)-symmetry, stabilized by intramolecular hydrogen bonds. Surprisingly, intermolecular hydrogen bonds between the macrocycles were not observed. (1)H NMR spectra suggest a C(2) symmetrical conformation of the octamer in solution al…
Novel antiproliferative chimeric compounds with marked histone deacetylase inhibitory activity.
2014
Given our interest in finding potential antitumor agents and in view of the multifactorial mechanistic nature of cancer, in the present work, taking advantage of the multifunctional ligands approach, new chimeric molecules were designed and synthesized by combining in single chemical entities structural features of SAHA, targeting histone deacetylases (HDACs), with substituted stilbene or terphenyl derivatives previously obtained by us and endowed with antiproliferative and pro-apoptotic activity. The new chimeric derivatives were characterized with respect to their cytotoxic activity and their effects on cell cycle progression on different tumor cell lines, as well as their HDACs inhibitio…
FSHD muscular dystrophy region gene 1 binds Suv4-20h1 histone methyltransferase and impairs myogenesis.
2013
Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant myopathy with a strong epigenetic component. It is associated with deletion of a macrosatellite repeat leading to over-expression of the nearby genes. Among them, we focused on FSHD region gene 1 (FRG1) since its over-expression in mice, Xenopus laevis and Caenorhabditis elegans, leads to muscular dystrophy-like defects, suggesting that FRG1 plays a relevant role in muscle biology. Here we show that, when over-expressed, FRG1 binds and interferes with the activity of the histone methyltransferase Suv4-20h1 both in mammals and Drosophila. Accordingly, FRG1 over-expression or Suv4-20h1 knockdown inhibits myogenesis. Moreov…
MOZ/TIF2-induced acute myeloid leukaemia in transgenic fish.
2008
The inv(8)(p11q13) chromosomal abnormality, described in acute myeloid leukaemias (AML), fuses the histone acetyl-transferase (HAT) MYST3 (MOZ) gene with another HAT gene, NCOA2 (TIF2). We generated a transgenic zebrafish in which the MYST3/NCOA2 fusion gene was expressed under control of the spi1 promoter. An AML developed in 2 of 180 MYST3/NCOA2-EGFP-expressing embryos, 14 and 26 months after injection of the fusion gene in a one-cell embryo, respectively. This leukaemia was characterised by an extensive invasion of kidneys by myeloid blast cells. This model, which is the first zebrafish model of AML, demonstrates the oncogenic potency of MYST3/NCOA2 fusion gene.
Functional characterization of human nucleosome assembly protein-2 (NAP1L4) suggests a role as a histone chaperone.
1997
Abstract Histones are thought to play a key role in regulating gene expression at the level of DNA packaging. Recent evidence suggests that transcriptional activation requires competition of transcription factors with histones for binding to regulatory regions and that there may be several mechanisms by which this is achieved. We have characterized a human nucleosome assembly protein, NAP-2, previously identified by positional cloning at 11p15.5, a region implicated in several disease processes including Wilms tumor (WT) etiology. The deduced amino acid sequence of NAP-2 indicates that it encodes a protein with a potential nuclear localization motif and two clusters of highly acidic residue…
Synergistic targeting of FLT3 mutations in AML via combined menin-MLL and FLT3 inhibition
2020
Abstract The interaction of menin (MEN1) and MLL (MLL1, KMT2A) is a dependency and provides a potential opportunity for treatment of NPM1-mutant (NPM1mut) and MLL-rearranged (MLL-r) leukemias. Concomitant activating driver mutations in the gene encoding the tyrosine kinase FLT3 occur in both leukemias and are particularly common in the NPM1mut subtype. In this study, transcriptional profiling after pharmacological inhibition of the menin-MLL complex revealed specific changes in gene expression, with downregulation of the MEIS1 transcription factor and its transcriptional target gene FLT3 being the most pronounced. Combining menin-MLL inhibition with specific small-molecule kinase inhibitors…
Redox signaling in acute pancreatitis
2015
Acute pancreatitis is an inflammatory process of the pancreatic gland that eventually may lead to a severe systemic inflammatory response. A key event in pancreatic damage is the intracellular activation of NF-κB and zymogens, involving also calcium, cathepsins, pH disorders, autophagy, and cell death, particularly necrosis. This review focuses on the new role of redox signaling in acute pancreatitis. Oxidative stress and redox status are involved in the onset of acute pancreatitis and also in the development of the systemic inflammatory response, being glutathione depletion, xanthine oxidase activation, and thiol oxidation in proteins critical features of the disease in the pancreas. On th…
Mir-661: A key Factor in Embryo-Maternal dialog With Potential Clinical Application to Predict Implantation Outcome?
2015
Implantation resulting in a full-term pregnancy is, by large, more than a passive process in which the developed conceptus is passively glued to the uterus through adhesive molecules. It is the result of a perfectly orchestrated dialog between a viable embryo and a receptive endometrium, through a mixture of paracrine and juxtacrine processes in which many key proteins and growth factors play fundamental roles (Pellicer et al., 2002.) Since their discovery, microRNAs have become prominent regulatory candidates, providing missing links for a few biological pathways in this process, although their exact role in human normal embryo formation and endometrial preparation for pregnancy remains un…