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FoxP1

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https://www.readbyqxmd.com/read/29212910/foxp1-negatively-regulates-t-follicular-helper-cell-differentiation-and-germinal-center-responses-by-controlling-cell-migration-and-ctla-4
#1
Bi Shi, Jianlin Geng, Yin-Hu Wang, Hairong Wei, Beth Walters, Wei Li, Xuerui Luo, Anna Stevens, Melanie Pittman, Bin Li, Sunnie R Thompson, Hui Hu
T follicular helper (Tfh) cells play an essential role in the formation of germinal centers (GC) and generation of high-affinity Abs. The homing of activated CD4+ T cells into B cell follicles and the involvement of key costimulatory and coinhibitory molecules are critical in controlling both the initiation and the magnitude of GC responses. Meanwhile, studies have shown that a high number of single clone B cells leads to intraclonal competition, which inhibits the generation of high-affinity Abs. Our previous work has shown that transcription factor Foxp1 is a critical negative regulator of Tfh cell differentiation...
December 6, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29141232/foxp1-promotes-embryonic-neural-stem-cell-differentiation-by-repressing-jagged1-expression
#2
Luca Braccioli, Stephin J Vervoort, Youri Adolfs, Cobi J Heijnen, Onur Basak, R Jeroen Pasterkamp, Cora H Nijboer, Paul J Coffer
Mutations in FOXP1 have been linked to neurodevelopmental disorders including intellectual disability and autism; however, the underlying molecular mechanisms remain ill-defined. Here, we demonstrate with RNA and chromatin immunoprecipitation sequencing that FOXP1 directly regulates genes controlling neurogenesis. We show that FOXP1 is expressed in embryonic neural stem cells (NSCs), and modulation of FOXP1 expression affects both neuron and astrocyte differentiation. Using a murine model of cortical development, FOXP1-knockdown in utero was found to reduce NSC differentiation and migration during corticogenesis...
November 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29138280/foxp1-regulation-of-neonatal-vocalizations-via-cortical-development
#3
Noriyoshi Usui, Daniel J Araujo, Ashwinikumar Kulkarni, Marissa Co, Jacob Ellegood, Matthew Harper, Kazuya Toriumi, Jason P Lerch, Genevieve Konopka
The molecular mechanisms driving brain development at risk in autism spectrum disorders (ASDs) remain mostly unknown. Previous studies have implicated the transcription factor FOXP1 in both brain development and ASD pathophysiology. However, the specific molecular pathways both upstream of and downstream from FOXP1 are not fully understood. To elucidate the contribution of FOXP1-mediated signaling to brain development and, in particular, neocortical development, we generated forebrain-specific Foxp1 conditional knockout mice...
November 14, 2017: Genes & Development
https://www.readbyqxmd.com/read/29122756/foxp1-expression-is-a-prognostic-biomarker-in-follicular-lymphoma-treated-with-rituximab-containing-regimens
#4
Anja Mottok, Vindi Jurinovic, Pedro Farinha, Andreas Rosenwald, Ellen Leich, German Ott, Heike Horn, Wolfram Klapper, Michael Boesl, Wolfgang Hiddemann, Christian Steidl, Joseph M Connors, Laurie H Sehn, Randy D Gascoyne, Eva Hoster, Oliver Weigert, Robert Kridel
Follicular lymphoma (FL) is a clinically and molecularly highly heterogeneous disease, yet prognostication relies predominantly on clinical tools. We recently demonstrated that integration of mutation status of seven genes, including EZH2 and MEF2B, improves risk stratification. We mined gene expression data to uncover genes that are differentially expressed in EZH2- and MEF2B-mutated cases. We focused on FOXP1 and assessed its protein expression by immunohistochemistry (IHC) in a total of 763 tissue biopsies...
November 9, 2017: Blood
https://www.readbyqxmd.com/read/29104627/upregulation-of-microrna-206-induces-apoptosis-of-vascular-smooth-muscle-cells-and-decreases-risk-of-atherosclerosis-through-modulating-foxp1
#5
Tao Xing, Lixin Du, Xianbo Zhuang, Liyong Zhang, Jiheng Hao, Jiyue Wang
Forkhead box protein subfamily P (FOXP) 1 has an important role in the control of gene transcription and is also reported to function as a tumor suppressor. The aim of the present study was to explore the regulatory mechanisms of atherosclerosis by investigating the function of microRNA-206 (miR-206) and the regulatory association between miR-206 and its potential target gene, FOXP1, in vascular smooth muscle cells (VSMCs). Bioinformatics tools were utilized to identify FOXP1 as a target of miR-206. Luciferase reporter analysis was used to confirm this relationship and to identify the miR-206 binding site in the FOXP1 3'-untranslated region...
November 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29098032/identification-of-mirna-and-genes-involving-in-osteosarcoma-by-comprehensive-analysis-of-microrna-and-copy-number-variation-data
#6
Tao Luo, Xiangli Yi, Wei Si
The aim of the present study was to understand the molecular mechanisms of osteosarcoma by comprehensive analysis of microRNA (miRNA/miR) and copy number variation (CNV) microarray data. Microarray data (GSE65071 and GSE33153) were downloaded from the Gene Expression Omnibus. In GSE65071, differentially expressed miRNAs between the osteosarcoma and control groups were calculated by the Limma package. Target genes of differentially expressed miRNAs were identified by the starBase database. For GSE33153, PennCNV software was used to perform the copy number variation (CNV) analysis...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29097500/a-bio-clinical-prognostic-model-using-myc-and-bcl2-predicts-outcome-in-relapsed-refractory-diffuse-large-b-cell-lymphoma
#7
Mark Bosch, Ariz Akhter, Bingshu E Chen, Adnan Mansoor, David Lebrun, David Good, Michael Crump, Lois Shepherd, David W Scott, Douglas A Stewart
The objective of this study was to create a bio-clinical model, based on clinical and molecular predictors of event-free and overall survival for relapsed/refractory diffuse large B-cell lymphoma patients treated on the Canadian Cancer Trials Group LY12 prospective study. Sufficient histologic material was available for 91 cases to create tissue microarrays and perform immunohistochemistry staining for CD10, BCL6, MUM1/IRF4, FOXP1, LMO2, BCL2, MYC, P53 and pySTAT3 expression. 67 cases had material sufficient for fluorescent in-situ hybridization for MYC and BCL2...
November 2, 2017: Haematologica
https://www.readbyqxmd.com/read/29090079/prospective-investigation-of-foxp1-syndrome
#8
Paige M Siper, Silvia De Rubeis, Maria Del Pilar Trelles, Allison Durkin, Daniele Di Marino, François Muratet, Yitzchak Frank, Reymundo Lozano, Evan E Eichler, Morgan Kelly, Jennifer Beighley, Jennifer Gerdts, Arianne S Wallace, Heather C Mefford, Raphael A Bernier, Alexander Kolevzon, Joseph D Buxbaum
BACKGROUND: Haploinsufficiency of the forkhead-box protein P1 (FOXP1) gene leads to a neurodevelopmental disorder termed FOXP1 syndrome. Previous studies in individuals carrying FOXP1 mutations and deletions have described the presence of autism spectrum disorder (ASD) traits, intellectual disability, language impairment, and psychiatric features. The goal of the present study was to comprehensively characterize the genetic and clinical spectrum of FOXP1 syndrome. This is the first study to prospectively examine the genotype-phenotype relationship in multiple individuals with FOXP1 syndrome, using a battery of standardized clinical assessments...
2017: Molecular Autism
https://www.readbyqxmd.com/read/29061638/motor-neurons-with-limb-innervating-character-in-the-cervical-spinal-cord-are-sculpted-by-apoptosis-based-on-the-hox-code-in-chick-embryo
#9
Katsuki Mukaigasa, Chie Sakuma, Tomoaki Okada, Shunsaku Homma, Takako Shimada, Keiji Nishiyama, Noboru Sato, Hiroyuki Yaginuma
In the developing chick embryo, a certain population of motor neurons (MNs) in the non-limb-innervating cervical spinal cord undergoes apoptosis between embryonic days 4 and 5. However, the characteristics of these apoptotic MNs remain undefined. Here, by examining the spatiotemporal profiles of apoptosis and MN subtype marker expression in normal or apoptosis-inhibited chick embryos, we found that this apoptotic population is distinguishable by Foxp1 expression. When apoptosis was inhibited, the survived Foxp1+ MNs showed characteristics of lateral motor column (LMC) neurons, which are of a limb-innervating subtype, suggesting that cervical Foxp1(+) MNs are the rostral continuation of LMC...
October 23, 2017: Development
https://www.readbyqxmd.com/read/29057879/deletion-of-3p13-14-locus-spanning-foxp1-to-shq1-cooperates-with-pten-loss-in-prostate-oncogenesis
#10
Haley Hieronymus, Phillip J Iaquinta, John Wongvipat, Anuradha Gopalan, Rajmohan Murali, Ninghui Mao, Brett S Carver, Charles L Sawyers
A multigenic locus at 3p13-14, spanning FOXP1 to SHQ1, is commonly deleted in prostate cancer and lost broadly in a range of cancers but has unknown significance to oncogenesis or prognosis. Here, we report that FOXP1-SHQ1 deletion cooperates with PTEN loss to accelerate prostate oncogenesis and that loss of component genes correlates with prostate, breast, and head and neck cancer recurrence. We demonstrate that Foxp1-Shq1 deletion accelerates prostate tumorigenesis in mice in combination with Pten loss, consistent with the association of FOXP1-SHQ1 and PTEN loss observed in human cancers...
October 20, 2017: Nature Communications
https://www.readbyqxmd.com/read/29018172/foxo1-and-foxp1-play-opposing-roles-in-regulating-the-differentiation-and-antitumor-activity-of-th9-cells-programmed-by-il-7
#11
Enguang Bi, Xingzhe Ma, Yong Lu, Maojie Yang, Qiang Wang, Gang Xue, Jianfei Qian, Siqing Wang, Qing Yi
Tumor-specific CD4(+) T helper 9 (TH9) cells, so-called because of their production of the cytokine interleukin-9 (IL-9), are a powerful effector T cell subset for cancer immunotherapy. We found that pretreatment of naïve CD4(+) T cells with IL-7 further enhanced their differentiation into TH9 cells and augmented their antitumor activity. IL-7 markedly increased the abundance of the histone acetyltransferase p300 by activating the STAT5 and PI3K-AKT-mTOR signaling pathways and promoting the acetylation of histones at the Il9 promoter...
October 10, 2017: Science Signaling
https://www.readbyqxmd.com/read/28978667/foxp1-in-forebrain-pyramidal-neurons-controls-gene-expression-required-for-spatial-learning-and-synaptic-plasticity
#12
Daniel J Araujo, Kazuya Toriumi, Christine O Escamilla, Ashwinikumar Kulkarni, Ashley G Anderson, Matthew Harper, Noriyoshi Usui, Jacob Ellegood, Jason P Lerch, Shari G Birnbaum, Haley O Tucker, Craig M Powell, Genevieve Konopka
Genetic perturbations of the transcription factor Forkhead Box P1 (FOXP1) are causative for severe forms of autism spectrum disorder that are often comorbid with intellectual disability. Recent work has begun to reveal an important role for FoxP1 in brain development, but the brain-region-specific contributions of Foxp1 to autism and intellectual disability phenotypes have yet to be determined fully. Here, we describe Foxp1 conditional knock-out (Foxp1cKO) male and female mice with loss of Foxp1 in the pyramidal neurons of the neocortex and the CA1/CA2 subfields of the hippocampus...
November 8, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28890397/regulated-expression-of-the-tp%C3%AE-isoform-of-the-human-t-prostanoid-receptor-by-the-tumour-suppressors-foxp1-and-nkx3-1-implications-for-the-role-of-thromboxane-in-prostate-cancer
#13
Aine G O'Sullivan, Sarah B Eivers, Eamon P Mulvaney, B Therese Kinsella
The prostanoid thromboxane (TX)A2 signals through the TPα and TPβ isoforms of T Prostanoid receptor (TP) that are transcriptionally regulated by distinct promoters termed Prm1 and Prm3, respectively, within the TBXA2R gene. We recently demonstrated that expression of TPα and TPβ is increased in PCa, differentially correlating with Gleason grade and with altered CpG methylation of the individual Prm1/Prm3 regions within the TBXA2R. The current study sought to localise the sites of CpG methylation within Prm1 and Prm3, and to identify the main transcription factors regulating TPβ expression through Prm3 in the prostate adenocarcinoma PC-3 and LNCaP cell lines...
September 8, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28884888/foxp1-haploinsufficiency-phenotypes-beyond-behavior-and-intellectual-disability
#14
Angela Myers, Christèle du Souich, Connie L Yang, Lior Borovik, Jill Mwenifumbo, Rosemarie Rupps, Causes Study, Anna Lehman, Cornelius F Boerkoel
The forkhead box (FOX) transcription factors have roles in development, carcinogenesis, metabolism, and immunity. In humans FOXP1 mutations have been associated with language and speech defects, intellectual disability, autism spectrum disorder, facial dysmorphisms, and congenital anomalies of the kidney and urinary tract. In mice, Foxp1 plays critical roles in development of the spinal motor neurons, lymphocytes, cardiomyocytes, foregut, and skeleton. We hypothesized therefore that mutations of FOXP1 affect additional tissues in some humans...
December 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28741757/equivalent-missense-variant-in-the-foxp2-and-foxp1-transcription-factors-causes-distinct-neurodevelopmental-disorders
#15
Elliot Sollis, Pelagia Deriziotis, Hirotomo Saitsu, Noriko Miyake, Naomichi Matsumoto, Mariëtte J V Hoffer, Claudia A L Ruivenkamp, Mariëlle Alders, Nobuhiko Okamoto, Emilia K Bijlsma, Astrid S Plomp, Simon E Fisher
The closely related paralogues FOXP2 and FOXP1 encode transcription factors with shared functions in the development of many tissues, including the brain. However, while mutations in FOXP2 lead to a speech/language disorder characterized by childhood apraxia of speech (CAS), the clinical profile of FOXP1 variants includes a broader neurodevelopmental phenotype with global developmental delay, intellectual disability, and speech/language impairment. Using clinical whole-exome sequencing, we report an identical de novo missense FOXP1 variant identified in three unrelated patients...
November 2017: Human Mutation
https://www.readbyqxmd.com/read/28735298/foxp1-related-intellectual-disability-syndrome-a-recognisable-entity
#16
Ilse Meerschaut, Daniel Rochefort, Nicole Revençu, Justine Pètre, Christina Corsello, Guy A Rouleau, Fadi F Hamdan, Jacques L Michaud, Jenny Morton, Jessica Radley, Nicola Ragge, Sixto García-Miñaúr, Pablo Lapunzina, Maria Palomares Bralo, Maria Ángeles Mori, Stéphanie Moortgat, Valérie Benoit, Sandrine Mary, Nele Bockaert, Ann Oostra, Olivier Vanakker, Milen Velinov, Thomy Jl de Ravel, Djalila Mekahli, Jonathan Sebat, Keith K Vaux, Nataliya DiDonato, Andrea K Hanson-Kahn, Louanne Hudgins, Bruno Dallapiccola, Antonio Novelli, Luigi Tarani, Joris Andrieux, Michael J Parker, Katherine Neas, Berten Ceulemans, An-Sofie Schoonjans, Darina Prchalova, Marketa Havlovicova, Miroslava Hancarova, Magdalena Budisteanu, Annelies Dheedene, Björn Menten, Patrick A Dion, Damien Lederer, Bert Callewaert
BACKGROUND: Mutations in forkhead box protein P1 (FOXP1) cause intellectual disability (ID) and specific language impairment (SLI), with or without autistic features (MIM: 613670). Despite multiple case reports no specific phenotype emerged so far. METHODS: We correlate clinical and molecular data of 25 novel and 23 previously reported patients with FOXP1 defects. We evaluated FOXP1 activity by an in vitro luciferase model and assessed protein stability in vitro by western blotting...
September 2017: Journal of Medical Genetics
https://www.readbyqxmd.com/read/28669662/characterization-and-functional-analysis-of-the-paralichthys-olivaceus-prdm1-gene-promoter
#17
Peizhen Li, Bo Wang, Dandan Cao, Yuezhong Liu, Quanqi Zhang, Xubo Wang
PR domain containing protein 1 (Prdm1) is a transcriptional repressor identified in various species and plays multiple important roles in immune response and embryonic development. However, little is known about the transcriptional regulation of the prdm1 gene. This study aims to characterize the promoter of Paralichthys olivaceus prdm1 (Po-prdm1) gene and determine the regulatory mechanism of Po-prdm1 expression. A 2000bp-long 5'-flanking region (translation initiation site designated as +1) of the Po-prdm1 gene was isolated and characterized...
October 2017: Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology
https://www.readbyqxmd.com/read/28642803/transcriptomic-profiles-of-aging-in-na%C3%A3-ve-and-memory-cd4-cells-from-mice
#18
Jackson Taylor, Lindsay Reynolds, Li Hou, Kurt Lohman, Wei Cui, Stephen Kritchevsky, Charles McCall, Yongmei Liu
BACKGROUND: CD4+ T cells can be broadly divided into naïve and memory subsets, each of which are differentially impaired by the aging process. It is unclear if and how these differences are reflected at the transcriptomic level. We performed microarray profiling on RNA derived from naïve (CD44(low)) and memory (CD44(high)) CD4+ T cells derived from young (2-3 month) and old (28 month) mice, in order to better understand the mechanisms of age-related functional alterations in both subsets...
2017: Immunity & Ageing: I & A
https://www.readbyqxmd.com/read/28555620/leukocyte-integrin-mac-1-regulates-thrombosis-via-interaction-with-platelet-gpib%C3%AE
#19
Yunmei Wang, Huiyun Gao, Can Shi, Paul W Erhardt, Alexander Pavlovsky, Dmitry A Soloviev, Kamila Bledzka, Valentin Ustinov, Liang Zhu, Jun Qin, Adam D Munday, Jose Lopez, Edward Plow, Daniel I Simon
Inflammation and thrombosis occur together in many diseases. The leukocyte integrin Mac-1 (also known as integrin αMβ2, or CD11b/CD18) is crucial for leukocyte recruitment to the endothelium, and Mac-1 engagement of platelet GPIbα is required for injury responses in diverse disease models. However, the role of Mac-1 in thrombosis is undefined. Here we report that mice with Mac-1 deficiency (Mac-1-/-) or mutation of the Mac-1-binding site for GPIbα have delayed thrombosis after carotid artery and cremaster microvascular injury without affecting parameters of haemostasis...
May 30, 2017: Nature Communications
https://www.readbyqxmd.com/read/28550168/reduced-expression-of-foxp1-as-a-contributing-factor-in-huntington-s-disease
#20
Anto Sam Crosslee Louis Sam Titus, Tanzeen Yusuff, Marlène Cassar, Elizabeth Thomas, Doris Kretzschmar, Santosh R D'Mello
Huntington's disease (HD) is an inherited neurodegenerative disease caused by a polyglutamine expansion in the huntington protein (htt). The neuropathological hallmark of HD is the loss of neurons in the striatum and, to a lesser extent, in the cortex. Foxp1 is a member of the Forkhead family of transcription factors expressed selectively in the striatum and the cortex. In the brain, three major Foxp1 isoforms are expressed: isoform-A (∼90 kDa), isoform-D (∼70 kDa), and isoform-C (∼50 kDa). We find that expression of Foxp1 isoform-A and -D is selectively reduced in the striatum and cortex of R6/2 HD mice as well as in the striatum of HD patients...
July 5, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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