Distribution of Histone3 Lysine 4 Trimethylation at T3-Responsive Loci in the Heart During Reversible Changes in Gene Expression

Expression in the adult heart of a number of cardiac genes, including the two genes comprising the cardiac Myosin heavy chain locus (Myh), is controlled by thyroid hormone (T3) levels, but there is minimal information concerning the epigenetic status of the genes when their expressions change. We fed mice normal chow or a Propyl thio uracil (PTU, an inhibitor of T3 production)-diet for 6 weeks, or the PTU diet for 6 weeks followed by normal chow for a further two weeks. Heart ventricles from these groups were then used for ChIP-seq analyses with an antibody to H3K4me3, a well documented epigenetic marker of gene activation. The resulting data show that, at the Myh7 locus, H3K4me3 modifications are induced primarily at 5’ transcribed region in parallel with increased expression of beta myosin heavy chain (MHC). At the Myh6 locus, decreases in H3K4me3 modifications occurred at the promoter and 5’ transcribed region. Extensive H3K4me3 modifications also occurred at the intergenic region between the two Myh genes which extended into the 3’ transcribed region of Myh7. The PTU-induced changes in H3K4me3 levels are, for the most part, reversible but are not invariably complete. We found full restoration of Myh6 gene expression upon PTU withdrawal, however the H3K4me3 pattern was only partially restored at Myh6, suggesting that full re-expression of Myh6 does not require that the H3K4me3 modifications return fully to the untreated conditions. Together, our data show that the H3K4me3 modification is an epigenetic marker closely associated with changes in Myh gene expression

Cross-enhancement of ANGPTL4 transcription by HIF1 alpha and PPAR beta/delta is the result of the conformational proximity of two response elements

BACKGROUND: Synergistic transcriptional activation by different stimuli has been reported along with a diverse array of mechanisms, but the full scope of these mechanisms has yet to be elucidated. RESULTS: We present a detailed investigation of hypoxia-inducible factor (HIF) 1 dependent gene expression in endothelial cells which suggests the importance of crosstalk between the peroxisome proliferator-activated receptor (PPAR) β/δ and HIF signaling axes. A migration assay shows a synergistic interaction between these two stimuli, and we identify angiopoietin-like 4 (ANGPTL4) as a common target gene by using a combination of microarray and ChIP-seq analysis. We profile changes of histone marks at enhancers under hypoxia, PPARβ/δ agonist and dual stimulations and these suggest that the spatial proximity of two response elements is the principal cause of the synergistic transcription induction. A newly developed quantitative chromosome conformation capture assay shows the quantitative change of the frequency of proximity of the two response elements. CONCLUSIONS: To the best of our knowledge, this is the first report that two different transcription factors cooperate in transcriptional regulation in a synergistic fashion through conformational change of their common target genes

Geographical Contents in Primary School : An Analysis of the English Geography Textbook “Collins Primary Geography”

In this study, we have analyzed the English geography textbook “Collins Primary Geography”, in order to clarify the characteristics of geographical contents in primary school. Results of this study are as follows: age (grade)-appropriate teaching through different process of leaning (awareness, understanding, cognition and value judgement) and physical, human, environmental geography and topography as a content. However, there are no contents across physical and human geography, one of the features of geography, in the textbook.本稿は，2016年度前期開講の地理認識内容学特講（由井担当）の一部をもとに，加筆・修正を加えたものである

TNFα signals through specialized factories where responsive coding and miRNA genes are transcribed: Specialized transcription factories

Tumour necrosis factor alpha (TNFα) is a potent cytokine that signals through nuclear factor kappa B (NFκB) to activate a subset of human genes. It is usually assumed that this involves RNA polymerases transcribing responsive genes wherever they might be in the nucleus. Using primary human endothelial cells, variants of chromosome conformation capture (including 4C and chromatin interaction analysis with paired-end tag sequencing), and fluorescence in situ hybridization to detect single nascent transcripts, we show that TNFα induces responsive genes to congregate in discrete ‘NFκB factories'. Some factories further specialize in transcribing responsive genes encoding micro-RNAs that target downregulated mRNAs. We expect all signalling pathways to contain this extra leg, where responding genes are transcribed in analogous specialized factories

Direct evidence for pitavastatin induced chromatin structure change in the KLF4 gene in endothelial cells.

Statins exert atheroprotective effects through the induction of specific transcriptional factors in multiple organs. In endothelial cells, statin-dependent atheroprotective gene up-regulation is mediated by Kruppel-like factor (KLF) family transcription factors. To dissect the mechanism of gene regulation, we sought to determine molecular targets by performing microarray analyses of human umbilical vein endothelial cells (HUVECs) treated with pitavastatin, and KLF4 was determined to be the most highly induced gene. In addition, it was revealed that the atheroprotective genes induced with pitavastatin, such as nitric oxide synthase 3 (NOS3) and thrombomodulin (THBD), were suppressed by KLF4 knockdown. Myocyte enhancer factor-2 (MEF2) family activation is reported to be involved in pitavastatin-dependent KLF4 induction. We focused on MEF2C among the MEF2 family members and identified a novel functional MEF2C binding site 148 kb upstream of the KLF4 gene by chromatin immunoprecipitation along with deep sequencing (ChIP-seq) followed by luciferase assay. By applying whole genome and quantitative chromatin conformation analysis {chromatin interaction analysis with paired end tag sequencing (ChIA-PET), and real time chromosome conformation capture (3C) assay}, we observed that the MEF2C-bound enhancer and transcription start site (TSS) of KLF4 came into closer spatial proximity by pitavastatin treatment. 3D-Fluorescence in situ hybridization (FISH) imaging supported the conformational change in individual cells. Taken together, dynamic chromatin conformation change was shown to mediate pitavastatin-responsive gene induction in endothelial cells

Letter to the Editor UDC: 616.24-006:616.592-006:616.714.1

kin metastasis to the scalp is very rare. This report describes metastasis to the scalp as the first manifestation of an unsuspected occult neoplasm. An 80-year-old woman presented with a four-week history of a slowly growing, non-ulcerated round solitary nodule in the scalp of the right temporal. The lesion was 2 cm in diameter, painless, and movable. Skin biopsy revealed metastasis from the lung adenocarcinoma. The chest film on admission revealed a large mass in the left upper lobe. CT scans showed extensive metastases to brain, liver, bone and both adrenal glands. Because of decreasing performance status of the patient, she received 250 mg gefitinib once daily. Although the response was evaluated as no change, she had symptomatic relief. The patient died of her disease 11 months later the diagnosis of skin metastasis. Skin metastasis occurs primarily near the primary lesion of interna

Pancoast's Syndrome due to Metastatic Carcinoma from the Stomach

We describe here a case of Pancoast's syndrome due to metastatic carcinoma from the stomach. Although obtaining a tissue diagnosis is often difficult with apical lesions, transbronchial or percutaneous needle biopsy is the procedure of choice since a certain number of these cases are potentially curable