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FoxP1

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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
#1
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
#2
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 fully determined. Here, we describe Foxp1 conditional knockout (Foxp1(cKO) ) male and female mice with loss of Foxp1 in the pyramidal neurons of the neocortex and the CA1/CA2 subfields of the hippocampus...
October 4, 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
#3
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
#4
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...
September 8, 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
#5
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
#6
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...
July 22, 2017: Journal of Medical Genetics
https://www.readbyqxmd.com/read/28669662/characterization-and-functional-analysis-of-the-paralichthys-olivaceus-prdm1-gene-promoter
#7
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
#8
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
#9
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
#10
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
https://www.readbyqxmd.com/read/28540026/meta-analysis-of-gwas-of-over-16-000-individuals-with-autism-spectrum-disorder-highlights-a-novel-locus-at-10q24-32-and-a-significant-overlap-with-schizophrenia
#11
(no author information available yet)
BACKGROUND: Over the past decade genome-wide association studies (GWAS) have been applied to aid in the understanding of the biology of traits. The success of this approach is governed by the underlying effect sizes carried by the true risk variants and the corresponding statistical power to observe such effects given the study design and sample size under investigation. Previous ASD GWAS have identified genome-wide significant (GWS) risk loci; however, these studies were of only of low statistical power to identify GWS loci at the lower effect sizes (odds ratio (OR) <1...
2017: Molecular Autism
https://www.readbyqxmd.com/read/28507505/protein-protein-interaction-among-the-foxp-family-members-and-their-regulation-of-two-target-genes-vldlr-and-cntnap2-in-the-zebra-finch-song-system
#12
Ezequiel Mendoza, Constance Scharff
The Forkhead transcription factor FOXP2 is implicated in speech perception and production. The avian homolog, FoxP2 contributes to song learning and production in birds. In human cell lines, transcriptional activity of FOXP2 requires homo-dimerization or dimerization with paralogs FOXP1 or FOXP4. Whether FoxP dimerization occurs in the brain is unknown. We recently showed that FoxP1, FoxP2 and FoxP4 (FoxP1/2/4) proteins are co-expressed in neurons of Area X, a song control region in zebra finches. We now report on dimer- and oligomerization of zebra finch FoxPs and how this affects transcription...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28471196/-the-importance-of-microrna-deregulation-in-the-molecular-pathogenesis-and-histological-transformation-of-follicular-lymphoma
#13
K Musilová, J Deván, L Zlámalíková, L Křen, H Móciková, V Procházka, J Mayer, M Trněný, A Janíková, M Mráz
BACKGROUND: Molecular pathogenesis of follicular lymphoma (FL) is characterized by substantial dysregulation of epigenetic regulators. Many cases of FL are associated with the aberrant expression of non-coding regulatory RNAs, namely microRNAs (miRNA). Here we studied changes in miRNA expression and their association with histological transformation of FL to diffuse large B-cell lymphoma (DLBCL). MATERIAL AND METHODS: To identify changes in miRNA levels during FL transformation we performed a global expression analysis of 377 miRNAs in 16 samples (8 pairs) from FL patients vs...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/28434006/unbiased-quantification-of-subplate-neuron-loss-following-neonatal-hypoxia-ischemia-in-a-rat-model
#14
Alexandra Mikhailova, Naveena Sunkara, Patrick S McQuillen
BACKGROUND: Cellular targets of neonatal hypoxia-ischemia (HI) include both oligodendrocyte and neuronal lineages with differences in the patterns of vulnerable cells depending upon the developmental stage at which the injury occurs. Injury to the developing white matter is a characteristic feature of human preterm brain injury. Data are accumulating, however, for neuronal injury in the developing cerebral cortex. In the most widely used rodent model of preterm HI brain injury, conflicting data have been reported regarding the sensitivity of subplate neurons to early neonatal HI, with some reports of selective vulnerability and others that find no increased loss of subplate neurons in comparison with other cortical layers...
2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28408745/sumoylation-of-foxp1-regulates-transcriptional-repression-via-ctbp1-to-drive-dendritic-morphogenesis
#15
Daniel L Rocca, Kevin A Wilkinson, Jeremy M Henley
Forkhead Box P (FOXP) transcriptional repressors play a major role in brain development and their dysfunction leads to human cognitive disorders. However, little is known about how the activity of these proteins is regulated. Here, we show that FOXP1 SUMOylation at lysine 670 is required for recruiting the co-repressor CtBP1 and transcriptional repression. FOXP1 SUMOylation is tightly controlled by neuronal activity, in which synapse to nucleus signalling, mediated via NMDAR and L-type calcium channels, results in rapid FOXP1 deSUMOylation...
April 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28384713/forkhead-box-protein-p1-is-dispensable-for-retina-but-essential-for-lens-development
#16
Haruna Suzuki-Kerr, Yukihiro Baba, Asano Tsuhako, Hideto Koso, Joseph D Dekker, Haley O Tucker, Hiroshi Kuribayashi, Sumiko Watanabe
Purpose: Forkhead box protein P1 (Foxp1) is a transcriptional repressor expressed in many tissues. We identified Foxp1 as a highly expressed gene in retinal progenitor cells and investigated its roles during eye development. Methods: Mouse eyes with Foxp1 gain- or loss-of-function were established in vitro and in vivo. Results: Foxp1 overexpression in retinal progenitor cells resulted in reduced rod and increased cone photoreceptors. However, retina-specific knockout of Foxp1 was not associated with retinal differentiation abnormalities...
April 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28344757/leveraging-blood-serotonin-as-an-endophenotype-to-identify-de-novo-and-rare-variants-involved-in-autism
#17
Rui Chen, Lea K Davis, Stephen Guter, Qiang Wei, Suma Jacob, Melissa H Potter, Nancy J Cox, Edwin H Cook, James S Sutcliffe, Bingshan Li
BACKGROUND: Autism spectrum disorder (ASD) is one of the most highly heritable neuropsychiatric disorders, but underlying molecular mechanisms are still unresolved due to extreme locus heterogeneity. Leveraging meaningful endophenotypes or biomarkers may be an effective strategy to reduce heterogeneity to identify novel ASD genes. Numerous lines of evidence suggest a link between hyperserotonemia, i.e., elevated serotonin (5-hydroxytryptamine or 5-HT) in whole blood, and ASD. However, the genetic determinants of blood 5-HT level and their relationship to ASD are largely unknown...
2017: Molecular Autism
https://www.readbyqxmd.com/read/28257525/foxp-in-tetrapoda-intrinsically-disordered-regions-short-linear-motifs-and-their-evolutionary-significance
#18
Lucas Henriques Viscardi, Luciana Tovo-Rodrigues, Pamela Paré, Nelson Jurandi Rosa Fagundes, Francisco Mauro Salzano, Vanessa Rodrigues Paixão-Côrtes, Claiton Henrique Dotto Bau, Maria Cátira Bortolini
The FOXP subfamily is probably the most extensively characterized subfamily of the forkhead superfamily, playing important roles in development and homeostasis in vertebrates. Intrinsically disorder protein regions (IDRs) are protein segments that exhibit multiple physical interactions and play critical roles in various biological processes, including regulation and signaling. IDRs in proteins may play an important role in the evolvability of genetic systems. In this study, we analyzed 77 orthologous FOXP genes/proteins from Tetrapoda, regarding protein disorder content and evolutionary rate...
January 2017: Genetics and Molecular Biology
https://www.readbyqxmd.com/read/28240601/foxp1-controls-mesenchymal-stem-cell-commitment-and-senescence-during-skeletal-aging
#19
Hanjun Li, Pei Liu, Shuqin Xu, Yinghua Li, Joseph D Dekker, Baojie Li, Ying Fan, Zhenlin Zhang, Yang Hong, Gong Yang, Tingting Tang, Yongxin Ren, Haley O Tucker, Zhengju Yao, Xizhi Guo
A hallmark of aged mesenchymal stem/progenitor cells (MSCs) in bone marrow is the pivot of differentiation potency from osteoblast to adipocyte coupled with a decrease in self-renewal capacity. However, how these cellular events are orchestrated in the aging progress is not fully understood. In this study, we have used molecular and genetic approaches to investigate the role of forkhead box P1 (FOXP1) in transcriptional control of MSC senescence. In bone marrow MSCs, FOXP1 expression levels declined with age in an inverse manner with those of the senescence marker p16INK4A...
April 3, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28219927/molecular-role-of-the-pax5-etv6-oncoprotein-in-promoting-b-cell-acute-lymphoblastic-leukemia
#20
Leonie Smeenk, Maria Fischer, Sabine Jurado, Markus Jaritz, Anna Azaryan, Barbara Werner, Mareike Roth, Johannes Zuber, Martin Stanulla, Monique L den Boer, Charles G Mullighan, Sabine Strehl, Meinrad Busslinger
PAX5 is a tumor suppressor in B-ALL, while the role of PAX5 fusion proteins in B-ALL development is largely unknown. Here, we studied the function of PAX5-ETV6 and PAX5-FOXP1 in mice expressing these proteins from the Pax5 locus. Both proteins arrested B-lymphopoiesis at the pro-B to pre-B-cell transition and, contrary to their proposed dominant-negative role, did not interfere with the expression of most regulated Pax5 target genes. Pax5-Etv6, but not Pax5-Foxp1, cooperated with loss of the Cdkna2a/b tumor suppressors in promoting B-ALL development...
March 15, 2017: EMBO Journal
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