scholarly journals Structural Insights into Stimulation of Ash1L's H3K36 Methyltransferase Activity through Mrg15 Binding

Structure ◽  
2019 ◽  
Vol 27 (5) ◽  
pp. 837-845.e3 ◽  
Author(s):  
Peini Hou ◽  
Chang Huang ◽  
Chao-Pei Liu ◽  
Na Yang ◽  
Tianshu Yu ◽  
...  
Keyword(s):  
Methyltransferase Activity ◽  
Structural Insights ◽  
Stimulation Of

Structural insights into the interactions of Polycomb Repressive Complex 2 with chromatin

2021 ◽  
Author(s):  
Akhil Gargey Iragavarapu ◽  
Liqi Yao ◽  
Vignesh Kasinath
Keyword(s):  
Target Genes ◽  
Histone H3 ◽  
Cell Type ◽  
Methyltransferase Activity ◽  
Post Translational Modifications ◽  
Polycomb Repressive Complex 2 ◽  
Polycomb Proteins ◽  
Polycomb Repressive Complexes ◽  
Structural Insights ◽  
Stimulation Of

Polycomb repressive complexes are a family of chromatin modifier enzymes which are critical for regulating gene expression and maintaining cell-type identity. The reversible chemical modifications of histone H3 and H2A by the Polycomb proteins are central to its ability to function as a gene silencer. PRC2 is both a reader and writer of the tri-methylation of histone H3 lysine 27 (H3K27me3) which serves as a marker for transcription repression, and heterochromatin boundaries. Over the last few years, several studies have provided key insights into the mechanisms regulating the recruitment and activation of PRC2 at Polycomb target genes. In this review, we highlight the recent structural studies which have elucidated the roles played by Polycomb cofactor proteins in mediating crosstalk between histone post-translational modifications and the recruitment of PRC2 and the stimulation of PRC2 methyltransferase activity.

Fine‐tuning the stimulation of MLL1 methyltransferase activity by a histone H3‐based peptide mimetic

2010 ◽  
Vol 25 (3) ◽  
pp. 960-967 ◽  
Author(s):  
Vanja Avdic ◽  
Pamela Zhang ◽  
Sylvain Lanouette ◽  
Anastassia Voronova ◽  
Ilona Skerjanc ◽  
...  
Keyword(s):  
Histone H3 ◽  
Fine Tuning ◽  
Methyltransferase Activity ◽  
Peptide Mimetic ◽  
Stimulation Of

scholarly journals JARID2 and AEBP2 regulate PRC2 activity in the presence of H2A ubiquitination or other histone modifications

2020 ◽  
Author(s):  
Vignesh Kasinath ◽  
Curtis Beck ◽  
Paul Sauer ◽  
Simon Poepsel ◽  
Jennifer Kosmatka ◽  
...  
Keyword(s):  
Zinc Fingers ◽  
Regulation Of Gene Expression ◽  
Inhibitory Effect ◽  
Histone H2a ◽  
Set Domain ◽  
Methyltransferase Activity ◽  
Post Translational Modifications ◽  
Nucleosomal Dna ◽  
Polycomb Repressive Complexes ◽  
Stimulation Of

ABSTRACTThe Polycomb repressive complexes PRC1 and PRC2 functionally interact to coordinate cell type identity by the epigenetic regulation of gene expression. It has been proposed that PRC2 is recruited to genomic loci via the recognition of PRC1-mediated mono-ubiquitination of histone H2A at lysine 119 (H2AK119ub1), but the mechanism of this process remains poorly understood. Here, we report the cryo-EM structure of human PRC2 with cofactors JARID2 and AEBP2 bound to a nucleosome substrate containing H2AK119ub1. We find that JARID2 and AEBP2 each interact with one of the two ubiquitin molecules in the nucleosome. A ubiquitin-interaction motif (UIM) in JARID2 is sandwiched between ubiquitin and the histone H2A-H2B acidic patch. Simultaneously, the tandem zinc-fingers of AEBP2 interact with the second ubiquitin and the histone H2A-H2B surface on the opposite side of the nucleosome. JARID2 plays a dual role in the H2AK119ub1 dependent stimulation of PRC2 through interactions with both EED via its K116 trimethylation and with the H2AK119-ubiquitin. AEBP2, on the other hand, appears to primarily serve as a scaffold contributing to the interaction between PRC2 and the H2AK119ub1 nucleosome. Our structure also provides a detailed visualization of the EZH2-nucleosome interface, revealing a segment of EZH2 (named “bridge helix”) that is stabilized as it bridges the EZH2(SET) domain, the H3 tail and the nucleosomal DNA. In addition to the role played by AEBP2 and JARID2 in PRC2 regulation by H2AK119ub1 recognition, we also observe that the presence of these cofactors partially overcomes the inhibitory effect that H3K4- and H3K36-trimethylation have on core PRC2. Together, our results reveal the central role played by cofactors JARID2 and AEBP2 in orchestrating the crosstalk between histone post-translational modifications and PRC2 methyltransferase activity.

scholarly journals Store-Operated Calcium Channels

2015 ◽  
Vol 95 (4) ◽  
pp. 1383-1436 ◽  
Author(s):  
Murali Prakriya ◽  
Richard S. Lewis
Keyword(s):  
Calcium Channels ◽  
Molecular Mechanisms ◽  
Major Pathway ◽  
Surface Receptors ◽  
Store Operate Calcium Entry ◽  
Channel Properties ◽  
Structural Insights ◽  
Unique Mechanism ◽  
Stimulation Of

Store-operated calcium channels (SOCs) are a major pathway for calcium signaling in virtually all metozoan cells and serve a wide variety of functions ranging from gene expression, motility, and secretion to tissue and organ development and the immune response. SOCs are activated by the depletion of Ca2+ from the endoplasmic reticulum (ER), triggered physiologically through stimulation of a diverse set of surface receptors. Over 15 years after the first characterization of SOCs through electrophysiology, the identification of the STIM proteins as ER Ca2+ sensors and the Orai proteins as store-operated channels has enabled rapid progress in understanding the unique mechanism of store-operate calcium entry (SOCE). Depletion of Ca2+ from the ER causes STIM to accumulate at ER-plasma membrane (PM) junctions where it traps and activates Orai channels diffusing in the closely apposed PM. Mutagenesis studies combined with recent structural insights about STIM and Orai proteins are now beginning to reveal the molecular underpinnings of these choreographic events. This review describes the major experimental advances underlying our current understanding of how ER Ca2+ depletion is coupled to the activation of SOCs. Particular emphasis is placed on the molecular mechanisms of STIM and Orai activation, Orai channel properties, modulation of STIM and Orai function, pharmacological inhibitors of SOCE, and the functions of STIM and Orai in physiology and disease.

scholarly journals Structural insights into the stimulation of S. pombe Dnmt2 catalytic efficiency by the tRNA nucleoside queuosine

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Sven Johannsson ◽  
Piotr Neumann ◽  
Alexander Wulf ◽  
Luisa M. Welp ◽  
Hans-Dieter Gerber ◽  
...  
Keyword(s):  
Catalytic Efficiency ◽  
Structural Insights ◽  
Stimulation Of

scholarly journals Stimulation of adipocyte phospholipid methyltransferase activity by phorbol 12-myristate 13-acetate. Differential regulation of phospholipid methyltransferase and lipolysis

1987 ◽  
Vol 241 (3) ◽  
pp. 917-921 ◽  
Author(s):  
K L Kelly
Keyword(s):  
Phorbol Esters ◽  
Inhibitory Effect ◽  
Differential Regulation ◽  
Hormone Sensitive Lipase ◽  
Regulatory Pathway ◽  
Methyltransferase Activity ◽  
Hormone Sensitive ◽  
Intracellular Target ◽  
Dose Dependent ◽  
Stimulation Of

The present studies demonstrate that treatment of rat adipocytes with the phorbol ester phorbol 12-myristate 13-acetate (PMA) causes a dose-dependent stimulation of phospholipid methyltransferase (PLMT) activity. The stimulatory effect of PMA was not additive with that of isoprenaline or forskolin. The sensitivity of stimulated PLMT activity to inhibition by insulin, however, was decreased in the presence of PMA. The inhibitory effect of a maximal concentration of insulin on PLMT was unchanged in the presence of PMA. In contrast with the effects on PLMT, the lipolytic response of adipocytes to isoprenaline and the anti-lipolytic response to insulin were unaffected by PMA. These data suggest that PLMT is, whereas hormone-sensitive lipase is not, an intracellular target for the action of PMA. The lack of effect of PMA on lipolysis suggests that PLMT and hormone-sensitive lipase can be regulated by separate mechanisms. Furthermore, phorbol esters do not interfere in the regulatory pathway whereby insulin inhibits PMLT or lipolysis.

Effects of 5-5'-Diphenyl-2-thiohydantoin (DPTH) and Thyroxine on the Ultrastructure and Chemical Composition of Rat Liver

1971 ◽  
Vol 29 ◽  
pp. 570-571
Author(s):  
E. A. Elfont ◽  
R. B. Tobin ◽  
D. G. Colton ◽  
M. A. Mehlman
Keyword(s):  
Chemical Composition ◽  
Rat Liver ◽  
Future Study ◽  
Mode Of Action ◽  
Liver Mitochondria ◽  
Rat Liver Mitochondria ◽  
Effective Inhibitor ◽  
Biochemical Effects ◽  
Glycerophosphate Dehydrogenase ◽  
Stimulation Of

Summary5,-5'-diphenyl-2-thiohydantoin (DPTH) is an effective inhibitor of thyroxine (T4) stimulation of α-glycerophosphate dehydrogenase in rat liver mitochondria. Because this finding indicated a possible tool for future study of the mode of action of thyroxine, the ultrastructural and biochemical effects of DPTH and/or thyroxine on rat liver mere investigated.Rats were fed either standard or DPTH (0.06%) diet for 30 days before T4 (250 ug/kg/day) was injected. Injection of T4 occurred daily for 10 days prior to sacrifice. After removal of the liver and kidneys, part of the tissue was frozen at -50°C for later biocheailcal analyses, while the rest was prefixed in buffered 3.5X glutaraldehyde (390 mOs) and post-fixed in buffered 1Z OsO4 (376 mOs). Tissues were embedded in Araldlte 502 and the sections examined in a Zeiss EM 9S.Hepatocytes from hyperthyroid rats (Fig. 2) demonstrated enlarged and more numerous mitochondria than those of controls (Fig. 1). Glycogen was almost totally absent from the cytoplasm of the T4-treated rats.

Gap junctions in the prothoracic glands of the tobacco hornworm, Manduca sexta

1992 ◽  
Vol 50 (1) ◽  
pp. 706-707
Author(s):  
Ji-da Dai ◽  
M. Joseph Costello ◽  
Lawrence I. Gilbert
Keyword(s):  
Gap Junctions ◽  
Small Molecules ◽  
Manduca Sexta ◽  
Freeze Fracture ◽  
Cell Communication ◽  
Cellular Level ◽  
Thin Sections ◽  
Prothoracic Glands ◽  
Polyhydroxylated Steroids ◽  
Stimulation Of

Insect molting and metamorphosis are elicited by a class of polyhydroxylated steroids, ecdysteroids, that originate in the prothoracic glands (PGs). Prothoracicotropic hormone stimulation of steroidogenesis by the PGs at the cellular level involves both calcium and cAMP. Cell-to-cell communication mediated by gap junctions may play a key role in regulating signal transduction by controlling the transmission of small molecules and ions between adjacent cells. This is the first report of gap junctions in the PGs, the evidence obtained by means of SEM, thin sections and freeze-fracture replicas.

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