Regulation of histone H4 acetylation in the CNS and defensive behavior command neurons of the mollusk Helix mediated by serotonin and neuropeptide FMRFamide

2018 ◽  
Vol 22 (5) ◽  
pp. 606-610
Author(s):  
L. N. Grinkevich ◽  
T. G. Zachepilo
Keyword(s):  
Defensive Behavior ◽  
Experimental Models ◽  
Behavior Patterns ◽  
Epigenetic Mechanisms ◽  
Histone H4 ◽  
Command Neurons ◽  
Inhibitory Pathways ◽  
Histone H4 Acetylation ◽  
The Right ◽  
Prolonged Response

Epigenetic mechanisms are commonly known to underlie memory formation. Presently, scientists’ attention is focused on changes in the levels of histone modifications (mainly acetylation and methylation) in the chromatin of CNS cells tested in various experimental models. Owing to their relatively simple CNSs, mollusks are among the most popular models. Our experiments were con-ducted with the molluskHelix lucorumbecause its CNS had been investigated in detail and most of its neurons had been proven to participate in the formation of different behavior patterns, including the prolonged response to various stimuli. This work concerns the influence of various effectors (serotonin and FMRFamide, associated with CNS activator and inhibitory pathways, respectively) on the acetylation of H4 histone in the subesopha­geal ganglion complex and in defensive behavior command neurons of the right and left parietal ganglia (RPa3/2 and LPa3/2) in the snail. Western blot analysis showed that FMRFamide inhibited histone H4 acetylation induced by serotonin in the subesophageal complex of CNS ganglia. How­ever, serotonin and FMRFamide cooperatively enhanced the induction of histone H4 acetylation in RPa3/2 defensive behavior command neurons. No changes were found in the counterpart LPa3/2. It is a new piece of evidence for functional asym­metry inHelix. The inhibitory pathways mediated by FMRFamide not only inhibit the activatory in­tracellular processes in the entire CNS but can also enhance them, as in RPa3/2 defensive behavior command neurons.

Possible Epigenetic Regulation of Functionally Opposing Groups of Genes Involved in Ex Vivo Expansion of Cord Blood Stem Cells

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3473-3473
Author(s):  
Sudhakar Baluchamy ◽  
Benjamin Petro ◽  
Hiroto Araki ◽  
Valerie Lindgren ◽  
Nadim Mahmud
Keyword(s):  
Stem Cells ◽  
Cord Blood ◽  
Epigenetic Regulation ◽  
Ex Vivo ◽  
Ex Vivo Expansion ◽  
Epigenetic Mechanisms ◽  
Histone H4 ◽  
Hematopoietic Stem ◽  
Transcript Levels ◽  
Histone H4 Acetylation

Abstract Recently, we have demonstrated that modifications of chromatin involving DNA methylation and histone acetylation events can change the fate of hematopoietic stem cells (HSC), likely as a result of altered gene expression patterns (Araki H et al. Blood 2007). In our current studies we have examined the epigenetic regulation of genes induced during the expansion of HSC by chromatin modifying agents [5aza-2-deoxycytidine (5azaD), trichostatin A (TSA)]. The expression of the polycomb repressing complex gene, enhancer of zeste homolog 2 (Ezh2) has been implicated in histone methylation and deacetylation. We observed a significant increase in the transcript levels of Ezh2 in addition to self-renewal genes HoxB4, Bmi1 and GATA-2 in 5azaD/TSA treated expanded human cord blood (CB) cells. Ezh2 overexpression has been shown to prevent HSC exhaustion in a murine model by chromatin stabilization. CB CD34+ cells expanded in 5azaD/TSA resulted in retention of relatively higher transcript levels of DNA methyltransferase (DNMT), DNMT1 and lower levels of DNMT3a and DNMT3b in CD34+CD90+ cells, the most primitive subpopulation, in contrast to the relatively mature CD34−CD90− cells. The retention of higher DNMT1, the maintenance methyltransferase, in the most primitive CD34+CD90+ cells may favor the chromosomal stability of expanded grafts. Cytogenetic analysis and DNA ploidy of expanded grafts were normal and the telomere length of expanded CB grafts did not reveal any significant alteration of their lengths in comparison to unmanipulated primary CB grafts. In order to explore the roles of epigenetic modifications on the differentiation of HSC during ex vivo expansion, we have also examined the transcript levels of genes associated with differentiation in 5azaD/TSA expanded cells in comparison to cells expanded in cytokines alone. Interestingly, the transcript levels of differentiation associated genes Pu.1 and GATA-1 decreased following 5azaD/TSA treatment. The lower transcript levels of differentiation inducing genes (Pu.1, GATA-1) and higher levels of self-renewing genes (Ezh2, HoxB4) in 5azaD/TSA expanded cells suggest a possible interaction among these functionally opposing groups of genes which are likely regulated by epigenetic mechanisms. By using a chromatin immunoprecipitation (ChIP) assay we observed significantly increased levels of histone H4 acetylation on the promoter sites of Hox-B4, Bmi-1, and GATA-2 and decreased levels of acetylation on the promoter sites of genes involved in differentiation (Pu.1, GATA-1) in 5azaD/TSA treated CB cells. The degree of histone H4 acetylation of these promoters sites directly correlated with the transcript levels of these genes as evidenced by real time quantitative PCR. Futhermore, silencing of HoxB4 by using short hairpin RNA (shRNA) during 5azaD/TSA mediated expansion resulted in about a 50% reduction in the expansion of CB cells in contrast to cells containing non-silencing control shRNA, indicating HoxB4 is required for HSC expansion. Understanding how the possible interactions between functionally opposing groups of genes regulating the expansion and differentiation of HSC is mediated by epigenetic mechanisms may further facilitate the optimization of ex vivo expansion strategies of CB grafts for therapeutic use.

scholarly journals Epigenetics and cytoprotection with heat acclimation

2016 ◽  
Vol 120 (6) ◽  
pp. 702-710 ◽  
Author(s):  
Michal Horowitz
Keyword(s):  
Transcription Factors ◽  
Heat Shock ◽  
Transcriptional Activation ◽  
Chromatin Condensation ◽  
Heat Acclimation ◽  
Heat Shock Factor 1 ◽  
Epigenetic Mechanisms ◽  
Histone H4 ◽  
Cross Tolerance ◽  
Histone H4 Acetylation

Studying “phenotypic plasticity” involves comparison of traits expressed in response to environmental fluctuations and aims to understand tolerance and survival in new settings. Reversible phenotypic changes that enable individuals to match their phenotype to environmental demands throughout life can be artificially induced, i.e., acclimation or occur naturally, i.e., acclimatization. The onset and achievement of acclimatory homeostasis are determined by molecular programs that induce the acclimated transcriptome. In heat acclimation, much evidence suggests that epigenetic mechanisms are powerful players in these processes. Epigenetic mechanisms affect the accessibility of the DNA to transcription factors, thereby regulating gene expression and controlling the phenotype. The heat-acclimated phenotype confers cytoprotection against novel stressors via cross-tolerance mechanisms, by attenuation of the initial damage and/or by accelerating spontaneous recovery through the release of help signals. This indispensable acclimatory feature has a memory and can be rapidly reestablished after the loss of acclimation and the return to the physiological preacclimated phenotype. The transcriptional landscape of the deacclimated phenotype includes constitutive transcriptional activation of epigenetic bookmarks. Heat shock protein (HSP) 70/HSP90/heat shock factor 1 memory protocol demonstrated constitutive histone H4 acetylation on hsp70 and hsp90 promotors. Novel players in the heat acclimation setup are poly(ADP-ribose)ribose polymerase 1 affecting chromatin condensation, DNA linker histones from the histone H1 cluster, and transcription factors associated with the P38 pathway. We suggest that these orchestrated responses maintain euchromatin and proteostasis during deacclimation and predispose to rapid reacclimation and cytoprotection. These mechanisms represent within-life epigenetic adaptations and cytoprotective memory.

scholarly journals IGF2 Is Up-regulated by Epigenetic Mechanisms in Hepatocellular Carcinomas and Is an Actionable Oncogene Product in Experimental Models

2016 ◽  
Vol 151 (6) ◽  
pp. 1192-1205 ◽  
Author(s):  
Iris Martinez-Quetglas ◽  
Roser Pinyol ◽  
Daniel Dauch ◽  
Sara Torrecilla ◽  
Victoria Tovar ◽  
...  
Keyword(s):  
Experimental Models ◽  
Epigenetic Mechanisms ◽  
Hepatocellular Carcinomas

scholarly journals Auditory cortical micro-networks show differential connectivity during voice and speech processing in humans

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Florence Steiner ◽  
Marine Bobin ◽  
Sascha Frühholz
Keyword(s):  
Speech Processing ◽  
Neural Circuits ◽  
Brain Activity ◽  
Inhibitory Pathways ◽  
Ac Networks ◽  
Directional Connectivity ◽  
The Right ◽  
Voice Processing ◽  
Differential Connectivity ◽  
Voice And Speech

AbstractThe temporal voice areas (TVAs) in bilateral auditory cortex (AC) appear specialized for voice processing. Previous research assumed a uniform functional profile for the TVAs which are broadly spread along the bilateral AC. Alternatively, the TVAs might comprise separate AC nodes controlling differential neural functions for voice and speech decoding, organized as local micro-circuits. To investigate micro-circuits, we modeled the directional connectivity between TVA nodes during voice processing in humans while acquiring brain activity using neuroimaging. Results show several bilateral AC nodes for general voice decoding (speech and non-speech voices) and for speech decoding in particular. Furthermore, non-hierarchical and differential bilateral AC networks manifest distinct excitatory and inhibitory pathways for voice and speech processing. Finally, while voice and speech processing seem to have distinctive but integrated neural circuits in the left AC, the right AC reveals disintegrated neural circuits for both sounds. Altogether, we demonstrate a functional heterogeneity in the TVAs for voice decoding based on local micro-circuits.

scholarly journals CBIO-19. LOW GLOBAL HISTONE H4 ACETYLATION LEVELS REVEAL CANDIDATE QUIESCENT CELL POPULATIONS IN GLIOMA AND DISTINGUISH TUMORS BY GRADE

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii19-ii19
Author(s):  
Anca Mihalas ◽  
Heather Feldman ◽  
Anoop Patel ◽  
Patrick Paddison
Keyword(s):  
Cell Types ◽  
Strand Break ◽  
Cell Cycle Gene ◽  
Low Grade ◽  
Histone H4 ◽  
Current Standard ◽  
A Genome ◽  
Histone H4 Acetylation

Abstract Current standard of care therapy for glioblastoma (GBM) includes cytoreduction followed by ablative therapies that target rapidly dividing cell types. However, the presence of quiescent-like/G0 states, therefore, represents a natural reservoir of tumor cells that are resistant to current treatments. Quiescence or G0 phase is a reversible state of “stasis” cells enter in response to developmental or environmental cues. To gain insight into how glioblastoma cells might regulate G0-like states, we performed a genome-wide CRISPR-Cas9 screen in patient-derived GBM stem-like cells (GSCs) harboring a G0-reporter to identify genes that when inhibited trap GSCs in G0-like states. Among the top screen hits were members of the Tip60/KAT5 histone acetyltransferase complex, which targets both histones (e.g., H4) and non-histone proteins for acetylation. NuA4 functions as a transcriptional activator, whose activities are coordinated with MYC in certain contexts, and also participates in DNA double-strand break repair by facilitating chromatin opening. However, currently little is known about the roles for NuA4 complex in GBM biology. Through modeling KAT5 function in GSC in vitro cultures and in vivo tumors, we find that KAT5 inhibition causes cells to arrest in a G0-like state with high p27 levels, G1-phase DNA content, low protein synthesis rates, low rRNA rates, lower metabolic rate, suppression of cell cycle gene expression, and low histone H4 acetylation. Interestingly, partial inhibition of KAT5 activity slows highly aggressive tumor growth, while increasing p27hi H4-aclow populations. Remarkably, we that low grade gliomas have significantly higher H4-aclow subpopulations and generally lower H4-ac levels than aggressive grade IV tumors. Taken together, our results suggest that NuA4/KAT5 activity may play a key role in quiescence ingress/egress in glioma and that targeting its activity in high grade tumors may effectively “down grade” them, thus, increase patient survival.

Serotonin stimulates GH secretion through a direct pituitary action: studies in hypophysectomized autografted animals and in perifused pituitaries

1986 ◽  
Vol 113 (3) ◽  
pp. 317-322 ◽  
Author(s):  
F. López ◽  
D. Gónzalez ◽  
E. Aguilar
Keyword(s):  
Plasma Volume ◽  
Direct Action ◽  
Experimental Models ◽  
Male Rats ◽  
Blood Samples ◽  
Kidney Capsule ◽  
Gh Secretion ◽  
Significant Release ◽  
The Right ◽  
Dose Dependent

Abstract. To analyze a possible direct action of serotonin (5-hydroxytryptamine) at pituitary level in GH secretion, two experimental models were used: hypophysectomized autografted rats and perifused pituitaries. Adult male rats were hypophysectomized and their own pituitaries placed under the right kidney capsule. Ten days later an intra-atrial cannula was inserted. The next day, blood samples were obtained before and every 10 min during a 2 h period after the injection of saline or 5-hydroxytryptamin (1 or 2 mg/kg iv). Plasma volume was replaced with saline. Both doses of 5-hydroxytryptamine elicit a strong release of GH, the effect being dose-dependent. In pituitaries perifused with 5-hydroxytryptamine (100 μm during 115 min or 1, 10 and 100 μm during 15 min), a significant release of GH was also observed. These results suggested that 5-hydroxytryptamine may stimulate GH secretion through a direct pituitary action.

scholarly journals Radiosensitization of Yeast Cells by Inhibition of Histone H4 Acetylation

2008 ◽  
Vol 170 (5) ◽  
pp. 618-627 ◽  
Author(s):  
Suisui Song ◽  
Kelly E. McCann ◽  
J. Martin Brown
Keyword(s):  
Yeast Cells ◽  
Histone H4 ◽  
Histone H4 Acetylation

scholarly journals Sites of Acetylation on Newly Synthesized Histone H4 Are Required for Chromatin Assembly and DNA Damage Response Signaling

2013 ◽  
Vol 33 (16) ◽  
pp. 3286-3298 ◽  
Author(s):  
Zhongqi Ge ◽  
Devi Nair ◽  
Xiaoyan Guan ◽  
Neha Rastogi ◽  
Michael A. Freitas ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Histone H3 ◽  
Model Organism ◽  
Strand Break ◽  
Chromatin Assembly ◽  
Histone H4 ◽  
Histone H4 Acetylation ◽  
Damage Response ◽  
A Site

The best-characterized acetylation of newly synthesized histone H4 is the diacetylation of the NH2-terminal tail on lysines 5 and 12. Despite its evolutionary conservation, this pattern of modification has not been shown to be essential for either viability or chromatin assembly in any model organism. We demonstrate that mutations in histone H4 lysines 5 and 12 in yeast confer hypersensitivity to replication stress and DNA-damaging agents when combined with mutations in histone H4 lysine 91, which has also been found to be a site of acetylation on soluble histone H4. In addition, these mutations confer a dramatic decrease in cell viability when combined with mutations in histone H3 lysine 56. We also show that mutation of the sites of acetylation on newly synthesized histone H4 results in defects in the reassembly of chromatin structure that accompanies the repair of HO-mediated double-strand breaks. This defect is not due to a decrease in the level of histone H3 lysine 56 acetylation. Intriguingly, mutations that alter the sites of newly synthesized histone H4 acetylation display a marked decrease in levels of phosphorylated H2A (γ-H2AX) in chromatin surrounding the double-strand break. These results indicate that the sites of acetylation on newly synthesized histones H3 and H4 can function in nonoverlapping ways that are required for chromatin assembly, viability, and DNA damage response signaling.

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