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https://www.readbyqxmd.com/read/28727928/vascular-senescence-and-ageing-a-role-for-the-meox-proteins-in-promoting-endothelial-dysfunction
#1
Josette Northcott, Michael Paul Czubryt, Jeffrey T Wigle
In the vascular system, ageing is accompanied by the accrual of senescent cells and is associated with an increased risk of vascular disease. Endothelial cell (EC) dysfunction is a hallmark of vascular disease and is characterized by decreased angiogenic potential, reduced nitric oxide bioavailability, impaired vasodilation, increased production of ROS and enhanced inflammation. In ECs, the major producer of nitric oxide is the endothelial nitric oxide synthase (eNOS) enzyme that is encoded by the NOS3 gene...
July 20, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28727279/characterization-of-two-homeodomain-transcription-factors-with-critical-but-distinct-roles-in-virulence-in-the-vascular-pathogen-verticillium-dahliae
#2
J L Sarmiento-Villamil, P Prieto, S J Klosterman, M D García-Pedrajas
Vascular wilt caused by Verticillium dahliae is a destructive disease that represents a chronic economic problem on crop production worldwide. In this work we characterized two new regulators of pathogenicity in this species. Vph1 (VDAG_06555) was identified in a candidate gene approach as a putative homolog of the transcription factor Ste12. Vhb1 (VDAG_08786), identified in a forward genetics approach, is similar to the homeobox transcription factor Htf1, reported as a regulator of conidiogenesis in several fungi...
July 20, 2017: Molecular Plant Pathology
https://www.readbyqxmd.com/read/28714688/design-of-a-chemical-probe-for-the-bromodomain-and-plant-homeodomain-finger-containing-brpf-family-of-proteins
#3
Niall Igoe, Elliott D Bayle, Cynthia Tallant, Oleg Fedorov, Julia C Meier, Pavel Savitsky, Catherine Rogers, Yannick Morias, Sarah Scholze, Helen Boyd, Danen Cunoosamy, David M Andrews, Anne Cheasty, Paul E Brennan, Susanne Müller, Stefan Knapp, Paul V Fish
The bromodomain and PHD finger-containing (BRPF) family are scaffolding proteins important for the recruitment of histone acetyltransferases of the MYST family to chromatin. Here we describe NI-57 (16) as new pan-BRPF chemical probe of the bromodomain (BRD) of the BRPFs. Inhibitor 16 preferentially bound the BRD of BRPF1 and BRD1 over BRPF3, whereas binding to BRD9 was weaker. 16 has excellent selectivity over non-class IV BRD proteins. Target engagement of BRPF1B and BRD1 with 16 was demonstrated in nanoBRET and FRAP assays...
July 17, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28710879/the-transcription-factor-pstste12-is-required-for-virulence-of-puccinia-striiformis-f-sp-tritici
#4
Xiaoguo Zhu, Wei Liu, Xiuling Chu, Qixiong Sun, Chenglong Tan, Qian Yang, Min Jiao, Jun Guo, Zhensheng Kang
Puccinia striiformis f. sp. tritici (Pst) is an obligate biotrophic fungus that causes extensive damage in wheat. The pathogen is now known to be a heteroecious fungus with an intricate life cycle containing sexual and asexual stages. Orthologs of the STE12 transcription factor that regulate mating and filamentation in Saccharomyces cerevisiae as well as virulence in other fungi has been extensively described. Because reliable transformation and gene disruption methods are lacking for Pst, knowledge about the function of its STE12 ortholog is limited...
July 15, 2017: Molecular Plant Pathology
https://www.readbyqxmd.com/read/28710291/two-types-of-etiological-mutation-in-the-limb-specific-enhancer-of-shh
#5
Takanori Amano, Tomoko Sagai, Ryohei Seki, Toshihiko Shiroishi
An enhancer named MFCS1 regulates Sonic hedgehog (Shh) expression in the posterior mesenchyme of limb buds. Several mutations in MFCS1 induce ectopic Shh expression in the anterior limb bud, and these result in preaxial polydactyly (PPD). However, the molecular basis of ectopic Shh expression remains elusive, although some mutations are known to disrupt the negative regulation of Shh expression in the anterior limb bud. Here, we analyzed the molecular mechanism of ectopic Shh expression in PPD including in a mouse mutation-hemimelic extra toes (Hx)-and in other MFCS1 mutations in different species...
July 14, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28692050/crosstalk-between-nrf2-and-hipk2-shapes-cytoprotective-responses
#6
L Torrente, C Sanchez, R Moreno, S Chowdhry, P Cabello, K Isono, H Koseki, T Honda, J D Hayes, A T Dinkova-Kostova, L de la Vega
Homeodomain interacting protein kinase-2 (HIPK2) is a member of the HIPK family of stress-responsive kinases that modulates cell growth, apoptosis, proliferation and development. HIPK2 has several well-characterised tumour suppressor roles, but recent studies suggest it can also contribute to tumour progression, although the underlying mechanisms are unknown. Herein, we have identified novel crosstalk between HIPK2 and the cytoprotective transcription factor NRF2. We show that HIPK2 is a direct transcriptional target of NRF2, identifying a functional NRF2 binding site in the HIPK2 gene locus and demonstrating for the first time a transcriptional mode of regulation for this kinase...
July 10, 2017: Oncogene
https://www.readbyqxmd.com/read/28686331/neural-tube-defects-in-waardenburg-syndrome-a-case-report-and-review-of-the-literature
#7
Joseph Hart, Kalpana Miriyala
Waardenburg syndrome type 1 (WS1) is an autosomal dominant genetic condition characterized by sensorineural deafness and pigment abnormalities, and is caused by variants in the PAX3 homeodomain. PAX3 variants have been associated with severe neural tube defects in mice and humans, but the frequency and clinical manifestations of this symptom remain largely unexplored in humans. Consequently, the role of PAX3 in human neural tube formation remains a study of interest, for clinical as well as research purposes...
July 7, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28676648/interactions-between-lhx3-and-isl1-family-lim-homeodomain-transcription-factors-are-conserved-in-caenorhabditis-elegans
#8
Mugdha Bhati, Estelle Llamosas, David A Jacques, Cy M Jeffries, Siavoush Dastmalchi, Nina Ripin, Hannah R Nicholas, Jacqueline M Matthews
LIM-Homeodomain (LIM-HD) transcription factors are highly conserved in animals where they are thought to act in a transcriptional 'LIM code' that specifies cell types, particularly in the central nervous system. In chick and mammals the interaction between two LIM-HD proteins, LHX3 and Islet1 (ISL1), is essential for the development of motor neurons. Using yeast two-hybrid analysis we showed that the Caenorhabditis elegans orthologs of LHX3 and ISL1, CEH-14 and LIM-7 can physically interact. Structural characterisation of a complex comprising the LIM domains from CEH-14 and a LIM-interaction domain from LIM-7 showed that these nematode proteins assemble to form a structure that closely resembles that of their vertebrate counterparts...
July 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28673717/distinctive-features-of-phox2b-expressing-neurons-in-the-rat-reticular-formation-dorsal-to-the-trigeminal-motor-nucleus
#9
Kouta Nagoya, Shiro Nakamura, Keiko Ikeda, Hiroshi Onimaru, Atsushi Yoshida, Kiyomi Nakayama, Ayako Mochizuki, Masaaki Kiyomoto, Fumihiko Sato, Kiyoshi Kawakami, Koji Takahashi, Tomio Inoue
Phox2b encodes a paired-like homeodomain-containing transcription factor essential for development of the autonomic nervous system. Phox2b-expressing (Phox2b(+)) neurons are present in the reticular formation dorsal to the trigeminal motor nucleus (RdV) as well as the nucleus of the solitary tract and parafacial respiratory group. However, the nature of Phox2b(+) RdV neurons is still unclear. We investigated the physiological and morphological properties of Phox2b(+) RdV neurons using postnatal day 2-7 transgenic rats expressing yellow fluorescent protein under the control of Phox2b...
July 1, 2017: Neuroscience
https://www.readbyqxmd.com/read/28671548/motoneurons-regulate-the-central-pattern-generator-during-drug-induced-locomotor-like-activity-in-the-neonatal-mouse
#10
Melanie Falgairolle, Joshua G Puhl, Avinash Pujala, Wenfang Liu, Michael James O'Donovan
Motoneurons are traditionally viewed as the output of the spinal cord that do not influence locomotor rhythmogenesis. We assessed the role of motoneuron firing during ongoing locomotor-like activity in neonatal mice expressing archaerhopsin-3 (Arch), halorhodopsin (eNpHR), or channelrhodopsin-2 (ChR2) in Choline acetyltransferase expressing neurons (ChAT(+)) or the LIM-homeodomain transcription factor Isl1(+) neurons. Illumination of the lumbar cord in mice expressing eNpHR or Arch in ChAT(+) or Isl1(+) neurons, depressed motoneuron discharge, transiently decreased the frequency, and perturbed the phasing of the locomotor-like rhythm...
July 3, 2017: ELife
https://www.readbyqxmd.com/read/28658625/in%C3%A2-vivo-regulation-of-the-zebrafish-endoderm-progenitor-niche-by-t-box-transcription-factors
#11
Andrew C Nelson, Stephen J Cutty, Saule N Gasiunas, Isabella Deplae, Derek L Stemple, Fiona C Wardle
T-box transcription factors T/Brachyury homolog A (Ta) and Tbx16 are essential for correct mesoderm development in zebrafish. The downstream transcriptional networks guiding their functional activities are poorly understood. Additionally, important contributions elsewhere are likely masked due to redundancy. Here, we exploit functional genomic strategies to identify Ta and Tbx16 targets in early embryogenesis. Surprisingly, we discovered they not only activate mesodermal gene expression but also redundantly regulate key endodermal determinants, leading to substantial loss of endoderm in double mutants...
June 27, 2017: Cell Reports
https://www.readbyqxmd.com/read/28653891/histone-deacetylase-5-promotes-the-migration-and-invasion-of-hepatocellular-carcinoma-via-increasing-the-transcription-of-hypoxia-inducible-factor-1%C3%AE-under-hypoxia-condition
#12
Ming Ye, Zejun Fang, Hongqian Gu, Rui Song, Jiangwei Ye, Hongzhang Li, Zhiguang Wu, Shenghui Zhou, Peng Li, Xiang Cai, Xiaokun Ding, Songshan Yu
Hypoxia plays a critical role in the progression and metastasis of hepatocellular carcinoma by activating the key transcription factor, hypoxia-inducible factor-1. This study aims to identify the novel mechanisms underlying the dysregulation of hypoxia-inducible factor-1α in hepatocellular carcinoma. We found that histone deacetylase 5, a highly expressed histone deacetylase in hepatocellular carcinoma, strengthened the migration and invasion of hepatocellular carcinoma cells under hypoxia but not normoxia condition...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28621470/the-pou-homeodomain-transcription-factor-poum2-and-broad-complex-isoform-2-transcription-factor-induced-by-20-hydroxyecdysone-collaboratively-regulate-vitellogenin-gene-expression-and-egg-formation-in-the-silkworm-bombyx-mori
#13
Y Lin, H Liu, C Yang, J Gu, G Shen, H Zhang, E Chen, C Han, Y Zhang, Y Xu, J Wu, Q Xia
Vitellogenin (Vg) is a source of nutrition for embryo development. Our previous study showed that the silkworm (Bombyx mori) transcription factor broad complex isoform 2 (BmBrC-Z2) regulates gene expression of the Vg gene (BmVg) by induction with 20-hydroxyecdysone (20E). However, the mechanism by which 20E regulates BmVg expression was not clarified. In this study, cell transfection experiments showed that the BmVg promoter containing the POU homeodomain transcription factor POUM2 (POUM2) and BrC-Z2 cis-response elements (CREs) showed a more significant response to 20E than that harbouring only the BrC-Z2 or POUM2 CRE...
June 16, 2017: Insect Molecular Biology
https://www.readbyqxmd.com/read/28621262/a-peptide-antagonist-of-prep1-p160-interaction-improves-ceramide-induced-insulin-resistance-in-skeletal-muscle-cells
#14
Ilaria Cimmino, Virginia Lorenzo, Francesca Fiory, Nunzianna Doti, Serena Ricci, Serena Cabaro, Antonietta Liotti, Luigi Vitagliano, Michele Longo, Claudia Miele, Pietro Formisano, Francesco Beguinot, Menotti Ruvo, Francesco Oriente
Prep1 is a homeodomain transcription factor belonging to the TALE protein family. Its overexpression affects glucose metabolism in several tissues. In particular, in skeletal muscle tissue the interaction of Prep1 with its cofactor p160 impairs GLUT4 expression and glucose uptake.In this study, we show that ceramides (C2cer), a class of lipids antagonizing insulin signalling, increase the levels of Prep1 and p160 in a dose and time-dependent fashion in L6 cells and induce their association by 80%. We find that C2cer exposure inhibits insulin receptor, IRS1 and Akt phosphorylation and reduces insulin-stimulated glycogen content and glucose uptake by 1...
May 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28617833/clinical-performance-validation-of-pitx2-dna-methylation-as-prognostic-biomarker-in-patients-with-head-and-neck-squamous-cell-carcinoma
#15
Verena Sailer, Heidrun Gevensleben, Joern Dietrich, Diane Goltz, Glen Kristiansen, Friedrich Bootz, Dimo Dietrich
BACKGROUND: Despite advances in combined modality therapy, outcomes in head and neck squamous cell cancer (HNSCC) remain dismal with five-year overall survival rates of less than 50%. Prognostic biomarkers are urgently needed to identify patients with a high risk of death after initial curative treatment. Methylation status of the paired-like homeodomain transcription factor 2 (PITX2) has recently emerged as a powerful prognostic biomarker in various cancers. In the present study, the clinical performance of PITX2 methylation was validated in a HNSCC cohort by means of an independent analytical platform (Infinium HumanMethylation450 BeadChip, Illumina, Inc...
2017: PloS One
https://www.readbyqxmd.com/read/28611467/phytohormonal-crosstalk-modulates-the-expression-of-mir166-165s-target-class-iii-hd-zips-and-kanadi-genes-during-root-growth-in-arabidopsis-thaliana
#16
Archita Singh, Shradha Roy, Sharmila Singh, Shabari Sarkar Das, Vibhav Gautam, Sandeep Yadav, Ashutosh Kumar, Alka Singh, Sukanya Samantha, Ananda K Sarkar
Both phytohormones and non-coding microRNAs (miRNAs) play important role in root development in Arabidopsis thaliana. Mature miR166/165 s, which are derived from precursor transcripts of concerned genes, regulate developmental processes, including leaf and root patterning, by targeting Class III HOMEODOMAIN LEUCINE-ZIPPER (HD-ZIP III) transcription factors (TFs). However, their regulation through hormones remained poorly understood. Here, we show that several phytohormones dynamically regulate the spatio-temporal expression pattern of miR166/165 and target HD-ZIP IIIs in developing roots...
June 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28607924/hipk2-overexpression-and-its-prognostic-role-in-human-papillomavirus-positive-tonsillar-squamous-cell-carcinoma
#17
Mi Jung Kwon, So Young Kang, Eun Sook Nam, Seong Jin Cho, Young-Soo Rho
Tonsillar squamous cell carcinomas (TSCCs) are the most common human papillomavirus- (HPV-) associated oropharyngeal cancers with poor prognosis. Homeodomain-interacting protein kinase 2 (HIPK2) is a central regulator of p53, which participates in apoptosis during the DNA damage response. HIPK2 is involved in HPV-associated uterine cervical and cutaneous carcinogenesis through its binding of HPV E6, thereby preventing apoptosis and contributing to tumor progression. However, its clinical and prognostic significance in TSCC remains unclear...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28607325/implication-of-phf2-expression-in-clear-cell-renal-cell-carcinoma
#18
Cheol Lee, Bohyun Kim, Boram Song, Kyung Chul Moon
Background: Clear cell renal cell carcinoma (CCRCC) is presumed to be associated with adipogenic differentiation. Histone modification is known to be important for adipogenesis, and the function of histone demethylase plant homeodomain finger 2 (PHF2) has been noted. In addition, PHF2 may act as a tumor suppressor via epigenetic regulation of p53 and is reported to be reduced in colon cancer and stomach cancer tissues. In this study, we examined PHF2 expression in CCRCC specimens by immunohistochemistry...
June 13, 2017: Journal of Pathology and Translational Medicine
https://www.readbyqxmd.com/read/28607179/phf6-regulates-phenotypic-plasticity-through-chromatin-organization-within-lineage-specific-genes
#19
Yadira M Soto-Feliciano, Jordan M E Bartlebaugh, Yunpeng Liu, Francisco J Sánchez-Rivera, Arjun Bhutkar, Abraham S Weintraub, Jason D Buenrostro, Christine S Cheng, Aviv Regev, Tyler E Jacks, Richard A Young, Michael T Hemann
Developmental and lineage plasticity have been observed in numerous malignancies and have been correlated with tumor progression and drug resistance. However, little is known about the molecular mechanisms that enable such plasticity to occur. Here, we describe the function of the plant homeodomain finger protein 6 (PHF6) in leukemia and define its role in regulating chromatin accessibility to lineage-specific transcription factors. We show that loss of Phf6 in B-cell leukemia results in systematic changes in gene expression via alteration of the chromatin landscape at the transcriptional start sites of B-cell- and T-cell-specific factors...
May 15, 2017: Genes & Development
https://www.readbyqxmd.com/read/28604763/proline-rich-homeodomain-protein-prh-hhex-is-a-suppressor-of-breast-tumour-growth
#20
R M Kershaw, D Roberts, J Wragg, A M Shaaban, E Humphreys, J Halsall, L Price, R Bicknell, K Gaston, P-S Jayaraman
Breast tumours progress from hyperplasia to ductal carcinoma in situ (DCIS) and invasive breast carcinoma (IBC). PRH/HHEX (proline-rich homeodomain/haematopoietically expressed homeobox) is a transcription factor that displays both tumour suppressor and oncogenic activity in different disease contexts; however, the role of PRH in breast cancer is poorly understood. Here we show that nuclear localization of the PRH protein is decreased in DCIS and IBC compared with normal breast. Our previous work has shown that PRH phosphorylation by protein kinase CK2 prevents PRH from binding to DNA and regulating the transcription of multiple genes encoding growth factors and growth factor receptors...
June 12, 2017: Oncogenesis
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