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https://www.readbyqxmd.com/read/28293170/an-insight-into-the-increasing-role-of-lncrnas-in-the-pathogenesis-of-gliomas
#1
REVIEW
Yuanliang Yan, Zhijie Xu, Zhi Li, Lunquan Sun, Zhicheng Gong
Long non-coding RNAs (LncRNAs) are essential epigenetic regulators with critical roles in tumor initiation and malignant progression. However, the roles and mechanisms of aberrantly expressed lncRNAs in the pathogenesis of gliomas are not fully understood. With the development of deep sequencing analyses, an extensive amount of functional non-coding RNAs has been discovered in glioma tissues and cell lines. Additionally, the contributions of several lncRNAs, such as Hox transcript antisense intergenic RNA, H19 and Colorectal neoplasia differentially expressed, previously reported to be involved in other pathogenesis and processes to the oncogenesis of glioblastoma are currently addressed...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28283040/functional-variation-in-allelic-methylomes-underscores-a-strong-genetic-contribution-and-reveals-novel-epigenetic-alterations-in-the-human-epigenome
#2
Warren A Cheung, Xiaojian Shao, Andréanne Morin, Valérie Siroux, Tony Kwan, Bing Ge, Dylan Aïssi, Lu Chen, Louella Vasquez, Fiona Allum, Frédéric Guénard, Emmanuelle Bouzigon, Marie-Michelle Simon, Elodie Boulier, Adriana Redensek, Stephen Watt, Avik Datta, Laura Clarke, Paul Flicek, Daniel Mead, Dirk S Paul, Stephan Beck, Guillaume Bourque, Mark Lathrop, André Tchernof, Marie-Claude Vohl, Florence Demenais, Isabelle Pin, Kate Downes, Hendrick G Stunnenberg, Nicole Soranzo, Tomi Pastinen, Elin Grundberg
BACKGROUND: The functional impact of genetic variation has been extensively surveyed, revealing that genetic changes correlated to phenotypes lie mostly in non-coding genomic regions. Studies have linked allele-specific genetic changes to gene expression, DNA methylation, and histone marks but these investigations have only been carried out in a limited set of samples. RESULTS: We describe a large-scale coordinated study of allelic and non-allelic effects on DNA methylation, histone mark deposition, and gene expression, detecting the interrelations between epigenetic and functional features at unprecedented resolution...
March 10, 2017: Genome Biology
https://www.readbyqxmd.com/read/28257976/the-pbx1-lupus-susceptibility-gene-regulates-cd44-expression
#3
Yuxin Niu, Mayami Sengupta, Anton A Titov, Seung-Chul Choi, Laurence Morel
PBX1-d is novel splice isoform of pre-B-cell leukemia homeobox 1 (PBX1) that lacks its DNA-binding and Hox-binding domains, and functions as a dominant negative. We have shown that PBX1-d expression in CD4(+) T cells is associated with systemic lupus erythematosus (SLE) in a mouse model as well as in human subjects. More specifically, PBX1-d expression leads to the production of autoreactive activated CD4+ T cells, a reduced frequency and function of Foxp3+ regulatory T (Treg) cells and an expansion of follicular helper T (Tfh) cells...
February 28, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28251884/mir-101-3p-suppresses-hox-transcript-antisense-rna-hotair-induced-proliferation-and-invasion-through-directly-targeting-srf-in-gastric-carcinoma-cells
#4
Xiaoyu Wu, Jin Zhou, Zhenfeng Wu, Che Chen, Jiayun Liu, Guannan Wu, Jing Zhai, Fukun Liu, Gang Li
MiR-101-3p was identified as a tumor suppressor in several cancers, but its exact role in gastric adenocarcinoma is still largely unknown. In this study, we found that, compared with the RGM-1 human normal gastric epithelial cells, miR-101-3p was significantly downregulated in all the 6 human gastric adenocarcinoma cell lines, including BGC-823, MNK-45, MGC-803, SGC-7901, AGS and HGC-27. Overexpression miR-101-3p suppressed both the proliferation and invasion of AGS gastric adenocarcinoma cells and knockdown of miR-101-3p displayed an opposite effect...
March 2, 2017: Oncology Research
https://www.readbyqxmd.com/read/28247551/characterization-of-chromosomal-abnormalities-in-pregnancy-losses-reveals-critical-genes-and-loci-for-human-early-development
#5
Yiyun Chen, Justin Bartanus, Desheng Liang, Hongmin Zhu, Amy M Breman, Janice L Smith, Hua Wang, Zhilin Ren, Ankita Patel, Pawel Stankiewicz, David S Cram, Sau Wai Cheung, Lingqian Wu, Fuli Yu
Detailed characterization of chromosomal abnormalities, a common cause for congenital abnormalities and pregnancy loss, is critical for elucidating genes for human fetal development. Here, 2186 product of conception (POC) samples were tested for copy number variations (CNVs) at two clinical diagnostic centers using whole genome sequencing and high-resolution chromosomal microarray analysis. We developed a new gene discovery approach to predict potential developmental genes and identified 275 candidate genes from CNVs detected from both datasets...
February 28, 2017: Human Mutation
https://www.readbyqxmd.com/read/28242784/mixed-lineage-leukemia-fusions-and-chromatin-in-leukemia
#6
Andrei V Krivtsov, Takayuki Hoshii, Scott A Armstrong
Recent studies have shown the importance of chromatin-modifying complexes in the maintenance of developmental gene expression and human disease. The mixed lineage leukemia gene (MLL1) encodes a chromatin-modifying protein and was discovered as a result of the cloning of translocations involved in human leukemias. MLL1 is a histone lysine 4 (H3K4) methyltransferase that supports transcription of genes that are important for normal development including homeotic (Hox) genes. MLL1 rearrangements result in expression of fusion proteins without H3K4 methylation activity but may gain the ability to recruit other chromatin-associated complexes such as the H3K79 methyltransferase DOT1L and the super elongation complex...
February 27, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/28223506/intragenic-cpg-islands-play-important-roles-in-bivalent-chromatin-assembly-of-developmental-genes
#7
Sun-Min Lee, Jungwoo Lee, Kyung-Min Noh, Won-Young Choi, Sejin Jeon, Goo Taeg Oh, Jeongsil Kim-Ha, Yoonhee Jin, Seung-Woo Cho, Young-Joon Kim
CpG, 5'-C-phosphate-G-3', islands (CGIs) have long been known for their association with enhancers, silencers, and promoters, and for their epigenetic signatures. They are maintained in embryonic stem cells (ESCs) in a poised but inactive state via the formation of bivalent chromatin containing both active and repressive marks. CGIs also occur within coding sequences, where their functional role has remained obscure. Intragenic CGIs (iCGIs) are largely absent from housekeeping genes, but they are found in all genes associated with organ development and cell lineage control...
March 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28220305/homeobox-wnt-and-fibroblast-growth-factor-signaling-is-augmented-during-alveogenesis-in-mice-lacking-superoxide-dismutase-3-extracellular
#8
Tania A Thimraj, Rahel L Birru, Ankita Mitra, Holger Schulz, George D Leikauf, Koustav Ganguly
Superoxide dismutase 3, extracellular (SOD3) polymorphisms have been implicated in reduced pulmonary function development and altered risk for chronic obstructive pulmonary disease. We previously reported that gene-targeted Sod3-/- mice have impaired lung function and human SOD3 variants are associated with reduced pulmonary function in children. Reduced lung SOD3 levels were reported in mice with lower lung function with the greatest difference occurring during alveogenesis phase [postnatal (P) days 14-28]...
February 20, 2017: Lung
https://www.readbyqxmd.com/read/28215941/intron-specific-patterns-of-divergence-of-lin-11-regulatory-function-in-the-c-elegans-nervous-system
#9
Siavash Amon, Bhagwati P Gupta
The diversity of neurons in the nervous system is specified by many genes, including those that encode transcription factors (TFs) and play crucial roles in coordinating gene transcription. To understand how the spatiotemporal expression of TF genes is regulated to generate neuronal diversity, we used one member of the LIM-Hox family, lin-11, as a model that is necessary for the differentiation of amphid neurons in the nematode C. elegans and a related species C. briggsae. We characterized transcriptional regulation of lin-11 and uncovered regulatory roles of two of the largest introns, intron 3 and intron 7...
April 1, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28188343/mll5-kmt2e-structure-function-and-clinical-relevance
#10
REVIEW
Xiaoming Zhang, Wisna Novera, Yan Zhang, Lih-Wen Deng
The mixed lineage leukemia (MLL) family of genes, also known as the lysine N-methyltransferase 2 (KMT2) family, are homologous to the evolutionarily conserved trithorax group that plays critical roles in the regulation of homeotic gene (HOX) expression and embryonic development. MLL5, assigned as KMT2E on the basis of its SET domain homology, was initially categorized under MLL (KMT2) family together with other six SET methyltransferase domain proteins (KMT2A-2D and 2F-2G). However, emerging evidence suggests that MLL5 is distinct from the other MLL (KMT2) family members, and the protein it encodes appears to lack intrinsic histone methyltransferase (HMT) activity towards histone substrates...
February 10, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28188179/new-insights-into-the-role-of-jmjd3-and-utx-in-axial-skeletal-formation-in-mice
#11
Chie Naruse, Shinwa Shibata, Masaru Tamura, Takayuki Kawaguchi, Kanae Abe, Kazushi Sugihara, Tomoaki Kato, Takumi Nishiuchi, Shigeharu Wakana, Masahito Ikawa, Masahide Asano
Jmjd3 and Utx are demethylases specific for lysine 27 of histone H3. Previous reports indicate that Jmjd3 is essential for differentiation of various cell types, such as macrophages and epidermal cells in mice, whereas Utx is involved in cancer and developmental diseases in humans and mice as well as Hox regulation in zebrafish and nematodes. Here, we report that Jmjd3, but not Utx, is involved in axial skeletal formation in mice. A Jmjd3 mutant embryo (Jmjd3(Δ18/Δ18)), but not a catalytically inactive Utx truncation mutant (Utx(-/y)), showed anterior homeotic transformation...
February 10, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28177890/long-noncoding-rna-hotair-promotes-metastasis-of-renal-cell-carcinoma-by-up-regulating-histone-h3k27-demethylase-jmjd3
#12
Ming Xia, Lv Yao, Qiaoxia Zhang, Feng Wang, Hongbin Mei, Xiaoqiang Guo, Weiren Huang
Long Noncoding RNAs (lncRNAs) are a kind of non-protein coding transcripts longer than 200 nucleotides, and play important roles in diverse biological processes, such as embryonic development and apoptosis. Homeobox (HOX) transcript antisense intergenic RNA (HOTAIR) is a negative prognostic factor in a variety of human cancers, such as breast, liver and lung cancers. HOTAIR can promote cancer cell metastasis by reprogramming chromatin organization. In the present study, HOTAIR expression was elevated in tissues of renal cell carcinoma compared to adjacent normal tissues, and positively correlated with metastasis (P<0...
February 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28121309/ultrabithorax-and-abdominal-a-specify-the-abdominal-appendage-in-a-dosage-dependent-manner-in-silkworm-bombyx-mori
#13
X L Tong, M Y Fu, P Chen, L Chen, Z H Xiang, C Lu, F Y Dai
In insects, there is a considerable diversity in leg distribution on the body, including number, segmental arrangement, morphological identity and consequent function, but the genetic basis for these differences is not well understood. Here by positional cloning, we showed that a ~355 kb region, including Bombyx mori Ultrabithorax (BmUbx) and abdominal-A (Bmabd-A), was responsible for the silkworm mutant Kh-extra-crescents-like (E(Kh)-l) that displayed additional thoracic limb-like legs on the first abdominal segment (A1) and occasionally on the second abdominal segment (A2)...
January 25, 2017: Heredity
https://www.readbyqxmd.com/read/28093668/molecular-characterization-of-hoxc8-gene-and-methylation-status-analysis-of-its-exon-1-associated-with-the-length-of-cashmere-fiber-in-liaoning-cashmere-goat
#14
Wen L Bai, Jiao J Wang, Rong H Yin, Yun L Dang, Ze Y Wang, Yu B Zhu, Yu Y Cong, Liang Deng, Dan Guo, Shi Q Wang, Shu H Yang, Hui L Xue
Homeobox protein Hox-C8 (HOXC8) is a member of Hox family. It is expressed in the dermal papilla of the skin and is thought to be associated with the hair inductive capacity of dermal papilla cells. In the present study, we isolated and characterized a full-length open reading frame of HOXC8 cDNA from the skin tissue of Liaoning cashmere goat, as well as, established a phylogenetic relationship of goat HOXC8 with that of other species. Also, we investigated the effect of methylation status of HOXC8 exon 1 at anagen secondary hair follicle on the cashmere fiber traits in Liaoning cashmere goat...
February 2017: Genetica
https://www.readbyqxmd.com/read/28087711/ctcf-mediated-topological-boundaries-during-development-foster-appropriate-gene-regulation
#15
Varun Narendra, Milica Bulajić, Job Dekker, Esteban O Mazzoni, Danny Reinberg
The genome is organized into repeating topologically associated domains (TADs), each of which is spatially isolated from its neighbor by poorly understood boundary elements thought to be conserved across cell types. Here, we show that deletion of CTCF (CCCTC-binding factor)-binding sites at TAD and sub-TAD topological boundaries that form within the HoxA and HoxC clusters during differentiation not only disturbs local chromatin domain organization and regulatory interactions but also results in homeotic transformations typical of Hox gene misregulation...
December 15, 2016: Genes & Development
https://www.readbyqxmd.com/read/28068897/neotenic-phenomenon-in-gene-expression-in-the-skin-of-foxn1-deficient-nude-mice-a-projection-for-regenerative-skin-wound-healing
#16
Anna Kur-Piotrowska, Marta Kopcewicz, Leslie P Kozak, Pawel Sachadyn, Anna Grabowska, Barbara Gawronska-Kozak
BACKGROUND: Mouse fetuses up to 16 day of embryonic development and nude (Foxn1- deficient) mice are examples of animals that undergo regenerative (scar-free) skin healing. The expression of transcription factor Foxn1 in the epidermis of mouse fetuses begins at embryonic day 16.5 which coincides with the transition point from scar-free to scar-forming skin wound healing. In the present study, we tested the hypothesis that Foxn1 expression in the skin is an essential condition to establish the adult skin phenotype and that Foxn1 inactivity in nude mice keeps skin in the immature stage resembling the phenomena of neoteny...
January 9, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28067428/hotair-role-in-melanoma-progression-and-its-identification-in-the-blood-of-patients-with-advanced-disease
#17
Monica Cantile, Giosuè Scognamiglio, Laura Marra, Gabriella Aquino, Chiara Botti, Maria Rosaria Falcone, Maria Gabriella Malzone, Giuseppina Liguori, Maurizio Di Bonito, Renato Franco, Paolo Antonio Ascierto, Gerardo Botti
OBJECTIVES: The molecular mechanisms responsible for the metastatic progression of melanoma have not been fully defined yet. We have recently shown that an important role in this process is certainly played by HOX genes, whose regulation is under control of particular non-coding RNAs, some of which are present within the HOX locus. HOTAIR is the most studied among them, whose aberrant expression is associated with the metastatic progression of many malignancies. The aim of this study was to verify the role played by HOTAIR in metastatic progression of melanoma and to evaluate the circulating levels of HOTAIR in the blood of patients with metastatic melanoma...
January 9, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28065741/essential-roles-for-cdx-in-murine-primitive-hematopoiesis
#18
Travis Brooke-Bisschop, Joanne G A Savory, Tanya Foley, Randy Ringuette, David Lohnes
The Cdx transcription factors play essential roles in primitive hematopoiesis in the zebrafish where they exert their effects, in part, through regulation of hox genes. Defects in hematopoiesis have also been reported in Cdx mutant murine embryonic stem cell models, however, to date no mouse model reflecting the zebrafish Cdx mutant hematopoietic phenotype has been described. This is likely due, in part, to functional redundancy among Cdx members and the early lethality of Cdx2 null mutants. To circumvent these limitations, we used Cre-mediated conditional deletion to assess the impact of concomitant loss of Cdx1 and Cdx2 on murine primitive hematopoiesis...
February 15, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28041967/cdx-is-crucial-for-the-timing-mechanism-driving-colinear-hox-activation-and-defines-a-trunk-segment-in-the-hox-cluster-topology
#19
Roel Neijts, Shilu Amin, Carina van Rooijen, Jacqueline Deschamps
Cdx and Hox transcription factors are important regulators of axial patterning and are required for tissue generation along the vertebrate body axis. Cdx genes have been demonstrated to act upstream of Hox genes in midgestation embryos. Here, we investigate the role of Cdx transcription factors in the gradual colinear activation of the Hox clusters. We found that Hox temporally colinear expression is severely affected in epiblast stem cells derived from Cdx null embryos. We demonstrate that after initiation of 3' Hox gene transcription, Cdx activity is crucial for H3K27ac deposition and for accessibility of cis-regulatory elements around the central - or 'trunk' - Hox genes...
February 15, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28026082/hox-genes-in-the-adult-skeleton-novel-functions-beyond-embryonic-development
#20
REVIEW
Danielle R Rux, Deneen M Wellik
Hox genes encode evolutionarily conserved transcription factors that control skeletal patterning in the developing embryo. They are expressed in regionally restricted domains and function to regulate the morphology of specific vertebral and long bone elements. Recent work has provided evidence that Hox genes continue to be regionally expressed in adult tissues. Fibroblasts cultured from adult tissues show broadly maintained Hox gene expression patterns. In the adult skeleton, Hox genes are expressed in progenitor-enriched populations of mesenchymal stem/stromal cells (MSCs), and genetic loss-of-function analyses have provided evidence that Hox genes function during the fracture healing process...
December 27, 2016: Developmental Dynamics: An Official Publication of the American Association of Anatomists
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