Faculty Opinions recommendation of RNF8 regulates active epigenetic modifications and escape gene activation from inactive sex chromosomes in post-meiotic spermatids.

Author(s):  
John Aitken
2012 ◽  
Vol 26 (24) ◽  
pp. 2737-2748 ◽  
Author(s):  
H.-S. Sin ◽  
A. Barski ◽  
F. Zhang ◽  
A. V. Kartashov ◽  
A. Nussenzweig ◽  
...  

PLoS Genetics ◽  
2018 ◽  
Vol 14 (2) ◽  
pp. e1007233 ◽  
Author(s):  
Shannel R. Adams ◽  
So Maezawa ◽  
Kris G. Alavattam ◽  
Hironori Abe ◽  
Akihiko Sakashita ◽  
...  

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Dane D Jensen ◽  
Yumei Feng

Increased expression of the brain (pro)renin receptor (PRR) contributes to the development of salt-sensitive hypertension (SSH). Yet, the mechanisms that drive this increase in PRR expression are not known. We previously reported an increase in histone 3 lysine 4 trimethylation (H3K4me3), an epigenetic marker for gene activation, on the PRR promoter in SSH mice. We hypothesized that the increase in brain PRR expression is driven by epigenetic modifications linked to high-salt intake. To test our hypothesis, C57Bl/6J mice were treated with Sham (sham pellet + tap water for drinking) or DOCA-salt (50mg DOCA pellet + 0.9% saline) with chronic intracerebroventricular (ICV) infusion of the epithelial sodium channel (ENaC) blocker Benzamil (2.64μg/day, 0.5μl/h) or aCSF for 3 days. Hypothalamic tissues were used to examine the chromatin modifiers activity (ng/h/mg of protein) responsible for the methylation or demethylation of H3K4 including the histone methyltransferase (HMT) and histone demethylase (HDM). Water intake and PRR mRNA level were monitored. In mice receiving ICV aCSF, DOCA-Salt treatment increased the activity of H3K4 HMT (18.5 ± 1.2 vs. 6.6 ± 0.3, P<0.001) and HDM (0.55 ± 0.03 vs. 0.37 ± 0.05, P<0.05) compared to Sham respectively. HMT activity was blunted by ICV infusion of Benzamil (14.2 ± 0.5, P<0.01) compared to ICV infusion of aCSF following 3 days of DOCA-salt treatment. Interestingly, HDM activity was further elevated with the treatment of ICV Benzamil compared to ICV infusion of aCSF (0.84 ± 0.03, P<0.01). ICV infusion of Benzamil also reduced the PRR mRNA levels in the hypothalamus of mice treated with DOCA-salt from (1.43 ± 0.09, P<0.05) to (1.07 ± 0.02 P>0.05) relative to Sham (1.00). In addition, the saline intake amount (ml/day) was lower (P<0.05) in mice receiving ICV infusion of Benzamil (17 ± 3) compared to ICV aCSF (32 ± 9) following DOCA-salt treatment. In summary, ICV infusion of Benzamil attenuates the elevation in HMT activity, water and sodium intake, and the PRR mRNA levels, while increasing HDM activity in DOCA-salt treated mice. We conclude the Benzamil-sensitive sodium channel, possibly ENaC, may be a key channel regulating the epigenetic modifications governing the increased expression of brain PRR in SSH.


Pathogens ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 132 ◽  
Author(s):  
Susu M. Zughaier ◽  
Corinne E. Rouquette-Loughlin ◽  
William M. Shafer

Epigenetic reprogramming in macrophages is termed trained innate immunity, which regulates immune tolerance and limits tissue damage during infection. Neisseria gonorrhoeae is a strict human pathogen that causes the sexually transmitted infection termed gonorrhea. Here, we report that this pathogen harbors a gene that encodes a histone deacetylase-like enzyme (Gc-HDAC) that shares high 3D-homology to human HDAC1, HDAC2 and HDAC8. A Gc-HDAC null mutant was constructed to determine the biologic significance of this gene. The results showed that WT gonococci reduced the expression of host defense peptides LL-37, HBD-1 and SLPI in macrophages when compared to its Gc-HDAC-deficient isogenic strain. The enrichment of epigenetic marks in histone tails control gene expression and are known to change during bacterial infections. To investigate whether gonococci exert epigenetic modifications on host chromatin, the enrichment of acetylated lysine 9 in histone 3 (H3K9ac) was investigated using the TLR-focused ChIP array system. The data showed that infection with WT gonococci led to higher H3K9ac enrichment at the promoters of pro-inflammatory mediators’ genes, many TLRs, adaptor proteins and transcription factors, suggesting gene activation when compared to infection with the Gc-HDAC-deficient mutant. Taken together, the data suggest that gonococci can exert epigenetic modifications on host cells to modulate certain macrophage defense genes, leading to a maladaptive state of trained immunity.


2016 ◽  
Vol 106 (3) ◽  
pp. e346-e347
Author(s):  
S.R. Adams ◽  
K.G. Alavattam ◽  
J.M. Sroga ◽  
M.A. Thomas ◽  
S.H. Namekawa

Author(s):  
Gregory J. Czarnota

Chromatin structure at the fundamental level of the nucleosome is important in vital cellular processes. Recent biochemical and genetic analyses show that nucleosome structure and structural changes are very active participants in gene expression, facilitating or inhibiting transcription and reflecting the physiological state of the cell. Structural states and transitions for this macromolecular complex, composed of DNA wound about a heterotypic octamer of variously modified histone proteins, have been measured by physico-chemical techniques and by enzyme-accessibility and are recognized to occur with various post-translational modifications, gene activation, transformation and with ionic-environment. In spite of studies which indicate various forms of nucleosome structure, all current x-ray and neutron diffraction studies have consistently resulted in only one structure, suggestive of a static conformation. In contrast, two-dimensional electron microscopy studies and three-dimensional reconstruction techniques have yielded different structures. These fundamental differences between EM and other ultrastructural studies have created a long standing quandary, which I have addressed and resolved using spectroscopic electron microscopy and statistical analyses of nucleosome images in a study of nucleosome structure with ionic environment.


1972 ◽  
Vol 71 (2_Suppla) ◽  
pp. S346-S368 ◽  
Author(s):  
Roger W. Turkington ◽  
Nobuyuki Kadohama

ABSTRACT Hormonal activation of gene transcription has been studied in a model system, the mouse mammary gland in organ culture. Transcriptive activity is stimulated in mammary stem cells by insulin, and in mammary alveolar cells by prolactin and insulin. Studies on the template requirement for expression of the genes for milk proteins demonstrate that DNA methylation has an obligatory dependence upon DNA synthesis, but is otherwise independent from hormonal regulation of mammary cell differentiation. Incorporation of 5-bromo-2′deoxyuridine into DNA selectively inhibits expression of the genes for specific milk proteins. Undifferentiated mammary cells activate the synthesis of specific acidic nuclear proteins when stimulated by insulin. Several of these induced acidic nuclear proteins are undetectable in unstimulated undifferentiated cells, but appear to be characteristic components of the nuclei of differentiated cells. These results indicate that mammary cell differentiation is associated with a change in acidic nuclear proteins, and they provide evidence to support the concept that acidic nuclear proteins may be involved in the regulation of gene transcription and of mammary cell differentiation.


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