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Forkhead box protein p1 is a transcriptional repressor of immune signaling in the CNS

ABSTRACT: Forkhead box protein P1 (Foxp1), a transcription factor showing highly enriched expression in the striatum, has been implicated in CNS development, but its role in the mature brain is unknown. In order to ascertain functional roles for Foxp1 in the CNS, we have identified gene targets for Foxp1 in vitro using gene expression microarrays and chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) assays. Transcriptome-wide analysis of Foxp1-transfected striatal cells revealed widespread expression changes of genes related to immune signaling, cancer, transcriptional regulation, and a curated Huntington’s disease (HD) signaling pathway. Integrating the microarray expression dataset with Foxp1 binding sequences determined from ChIP-seq analysis resulted in 75 direct targets of Foxp1, which included Foxp1 itself, which were also related to immune processes and the category “genetic disorder”. These findings demonstrate that Foxp1 is a primary transcriptional repressor of immunological-related gene expression in striatal cells.

ORGANISM(S): Mus musculus

PROVIDER: GSE31560 | GEO | 2011/11/01

SECONDARY ACCESSION(S): PRJNA145685

REPOSITORIES: GEO

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Forkhead box protein p1 is a transcriptional repressor of immune signaling in the CNS

Project description:Forkhead box protein P1 (Foxp1), a transcription factor showing highly enriched expression in the striatum, has been implicated in CNS development, but its role in the mature brain is unknown. In order to ascertain functional roles for Foxp1 in the CNS, we have identified gene targets for Foxp1 in vitro using gene expression microarrays and chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) assays. Transcriptome-wide analysis of Foxp1-transfected striatal cells revealed widespread expression changes of genes related to immune signaling, cancer, transcriptional regulation, and a curated Huntington’s disease (HD) signaling pathway. Integrating the microarray expression dataset with Foxp1 binding sequences determined from ChIP-seq analysis resulted in 75 direct targets of Foxp1, which included Foxp1 itself, which were also related to immune processes and the category “genetic disorder”. These findings demonstrate that Foxp1 is a primary transcriptional repressor of immunological-related gene expression in striatal cells. n=3 wt STHdh striatal cells and n=3 Foxp1-transfected STHdh striatal cells

2011-11-01 | E-GEOD-31560 | biostudies-arrayexpress

Foxp1 drives striatal projection neuron specification and organization via cell-type specific mechanism

Project description:The molecular mechanisms that underlie striatal development and organization remain largely unknown. Here, we show that Foxp1, a transcription factor strongly linked to autism and intellectual disability, regulates organizational features of striatal circuitry in a cell-type dependent fashion. Using single-cell RNA-sequencing, we examine the cellular diversity of the early postnatal striatum and demonstrate that Foxp1 specifies a subpopulation of indirect pathway spiny projection neurons (iSPNs) while maintaining the striosome-matrix architecture through molecular mechanisms mediated by direct pathway spiny projection neurons (dSPNs). Functionally, Foxp1 alters striatal projection patterns both cell-autonomously and non-autonomously. We connect these changes in striatal circuitry to distinct behavioral deficits relevant to phenotypes described in patients with FOXP1 loss-of-function mutations. These data reveal novel cell-type specific transcriptional mechanisms underlying distinct features of striatal circuitry and identify Foxp1 as a key regulator of striatal development

2020-04-13 | GSE125290 | GEO

The forkhead transcription factor FOXP1 profile in B-cells and B-cell lymphoma cell lines

Project description:Expression of the forkhead transcription factor FOXP1 is essential for early B cell development, whereas downregulation of FOXP1 at the germinal center (GC) stage is required for GC B cell function. Aberrantly high FOXP1 expression is frequently observed in diffuse large B cell lymphoma (DLBCL) and mucosa-associated lymphoid tissue (MALT) lymphoma, being associated with poor prognosis. Here, by gene expression microarray [GSE51382] and quantitative RT-PCR analysis upon ectopic overexpression of FOXP1 in primary human memory B cells (MBCs) and B-cell lines, combined with chromatin immunoprecipitation-sequencing (ChIP-seq), we established that FOXP1 directly represses expression of PRDM1, IRF4, and XBP1, transcriptional master regulators of plasma cell (PC) differentiation. In accordance, FOXP1 is prominently expressed in primary human naive and MBCs but expression strongly decreases during plasma PC differentiation. Moreover, as compared to IgM+ MBCs, IgG+ MBCs combine lower expression of FOXP1 with an enhanced intrinsic PC differentiation propensity, and constitutive (over)expression of FOXP1 in B cell lines and primary human MBCs represses their ability to differentiate into PCs. Taken together, our data indicate that proper control of FOXP1 expression plays a critical role in PC differentiation, whereas aberrant overexpression of FOXP1 might contribute to lymphomagenesis by blocking terminal B cell differentiation. OXP1 ChIP-seq profile in primary human memory B cells (MBCs) and B-cell lines

2015-05-19 | E-GEOD-69009 | biostudies-arrayexpress

Gene expression in the striatum of Nestin-Cre (Foxp1-/-) mice in comparison to WT animals at embryonic day (E)18.5

Project description:To define the genes and pathways which are influenced by Foxp1 in the striatum at embryonic stage (E)18.5 we performed a microarray expression study comparing gene expression in striatal tissue from WT and Nestin-Cre (Foxp1-/-) animals.

2019-10-03 | GSE138337 | GEO

The forkhead transcription factor FOXP1 profile in B-cells and B-cell lymphoma cell lines

2015-05-19 | GSE69009 | GEO

FOXP1 orchestration of ASD-relevant signaling pathways.

Project description:Mutations in the gene encoding the transcription factor forkhead box P1 or FOXP1 occur in patients with neurodevelopmental disorders, including autism. However, the function of FOXP1 in the brain remains mostly unknown. Here, we identify the gene expression program regulated by FoxP1 in both human neural cells and mouse brain and demonstrate a conserved role for FOXP1 transcriptional regulation of autism and Fragile X Mental Retardation Protein (FMRP) mediated pathways. Coexpression networks support a role for Foxp1 in neuronal activity, and we show that Foxp1 is necessary for neuronal excitability. Using a Foxp1 mouse model, we observe defects in ultrasonic vocalizations. This behavioral phenotype is reflected at the genomic level as striatal Foxp1-regulated overlap with genes known to be important in rodent vocalizations. These data support an integral role for FOXP1 in regulating signaling pathways vulnerable in developmental disorders and the specific regulation of pathways important for vocal communication. We carried out RNA-sequencing (RNA-seq) and ChIP-sequencing of human neural progenitors cells. We carried out RNA-sequencing (RNA-seq) of mouse striatal tissue, mouse hippocampal tissue and mouse cortical tissue. For the RNA-seq, four indipendent replicates were used for the neural progenitor cells and mouse tissues. For the Chip-seq, a single neural progenitor cell line was used.

2015-10-26 | E-GEOD-62718 | biostudies-arrayexpress

Upregulated forkhead-box A3 elevates the expression of forkhead-box A1 and forkhead-box A2 to promote metastasis in esophageal cancer.

Project description: Not available

| S-EPMC6444456 | biostudies-literature

FOXP1 orchestration of ASD-relevant signaling pathways.

2015-10-26 | GSE62718 | GEO

Forkhead box protein p1 is a transcriptional repressor of immune signaling in the CNS: implications for transcriptional dysregulation in Huntington disease.

Project description: Not available

| S-EPMC3384380 | biostudies-literature

Forkhead Box F1 (FOXF1) represses fibroblast functions relevant to fibrogenesis

Project description:Aberrant expression of master phenotype regulators by lung fibroblasts may play a central role in idiopathic pulmonary fibrosis (IPF). Interrogating IPF fibroblast transcriptome datasets, we identified Forkhead Box F1 (FOXF1), a DNA-binding protein required for lung development, as a candidate actor in IPF. Thus, we determined FOXF1 expression levels in fibroblasts cultured from normal or IPF lungs in vitro, and explored FOXF1 functions in these cells using transient and stable loss-of-function and gain-of-function models. FOXF1 mRNA and protein were expressed at higher levels in IPF compared with controls. In normal lung fibroblasts, FOXF1 repressed key fibroblast functions such as proliferation, survival, and expression of collagen-1 (COL1) and actin related protein 2/3 complex, subunit 2 (ARPC2). ARPC2 knockdown mimicked FOXF1 overexpression with regard to proliferation and COL1 expression. FOXF1 expression was induced by the antifibrotic mediator prostaglandin E2 (PGE2). Ex vivo, FOXF1 knockdown conferred CCL-210 lung fibroblasts the ability to implant and survive in uninjured mouse lungs. In IPF lung fibroblasts, FOXF1 regulated COL1 but not ARPC2 expression. In conclusion, FOXF1 functions and regulation were consistent with an antifibrotic role in lung fibroblasts. Higher FOXF1 levels in IPF fibroblasts may thus participate in a compensatory response to fibrogenesis. Lung fibroblasts derived from 4 different IPF patients (P313, P355, P375 and P426) were transiently transfected with pcfoxf1 or control pcDNA3.1-constructs. Total RNAs were extracted 24 h after transfection and hybridized on microarrays. One color experiment with 2 experimental conditions: pcfoxf1 and pcDNA3.1

2014-10-01 | E-GEOD-52612 | biostudies-arrayexpress

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