Molecular networks of the FOXP2 transcription factor in the brain

Hoed, Joery den; Devaraju, Karthikeyan; Fisher, Simon E.

doi:10.15252/embr.202152803

Cited by 29 publications

(20 citation statements)

References 182 publications

(261 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…FOXP2 expression in microglia may be unique to humans compared to other primates 114 . Thus, downregulation of the FOXP2 transcription factor gene regulatory module in human microglia may link the genetic risk of OUD to other traits, including risk-taking behaviors 115 , and neurodevelopmental processes 116 .…”

Section: Resultsmentioning

confidence: 99%

Single nuclei transcriptomics in human and non-human primate striatum implicates neuronal DNA damage and proinflammatory signaling in opioid use disorder

Phan

Ray

Xue

et al. 2023

Preprint

View full text Add to dashboard Cite

The striatum in the brain is involved in various behavioral functions, including reward, and disease processes, such as opioid use disorder (OUD). Further understanding of the role of striatal subregions in reward behaviors and their potential associations with OUD requires molecular identification of specific striatal cell types in human brain. The human striatum contains subregions based on different anatomical, functional, and physiological properties, with the dorsal striatum further divided into caudate and putamen. Both caudate and putamen are associated with alterations in reward processing, formation of habits, and development of negative affect states in OUD. Using single nuclei RNA-sequencing of human postmortem caudate and putamen, we identified canonical neuronal cell types in striatum (e.g.,dopamine receptor 1 or 2 expressing neurons, D1 or D2) and less abundant subpopulations, including D1/D2 hybrid neurons and multiple classes of interneurons. By comparing unaffected subjects to subjects with OUD, we found neuronal-specific differences in pathways related to neurodegeneration, interferon response, and DNA damage. DNA damage markers were also elevated in striatal neurons of rhesus macaques following chronic opioid administration. We identified sex-dependent differences in the expression of stress-induced transcripts (e.g., FKBP5) among astrocytes and oligodendrocytes from female subjects with OUD. Thus, we describe striatal cell types and leverage these data to gain insights into molecular alterations in human striatum associated with opioid addiction.

show abstract

Section: Resultsmentioning

confidence: 99%

Single nuclei transcriptomics in human and non-human primate striatum implicates neuronal DNA damage and proinflammatory signaling in opioid use disorder

Phan

Ray

Xue

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…As a transcription factor, FOXP2 is considered to be a transcription suppressor in most cases 34 . By using the ChIPBase database, we identified a potential FOXP2 binding site in the KDM5A promoter region.…”

Section: Discussionmentioning

confidence: 99%

“…As a transcription factor, FOXP2 is considered to be a transcription suppressor in most cases. 34 By using the ChIPBase database, we identified a potential FOXP2 binding site in the KDM5A promoter region. Subsequent double luciferase reporter gene and ChIP assays verified the binding of FOXP2 to the KDM5A promoter region.…”

Section: Overexpression Of Foxp2 Hindered Hcc Tumorigenesis In Vivomentioning

confidence: 99%

FOXP2 suppresses the proliferation, invasion, and aerobic glycolysis of hepatocellular carcinoma cells by regulating the KDM5A/FBP1 axis

Yan,

Sun,

Chen

et al. 2023

Environmental Toxicology

View full text Add to dashboard Cite

The Warburg effect is the preference of cancer cells to use glycolysis rather than oxidative phosphorylation to generate energy. Accumulating evidence suggests that aerobic glycolysis is widespread in hepatocellular carcinoma (HCC) and closely related to tumorigenesis. The purpose of this study was to investigate the role and mechanism of forkhead box P2 (FOXP2) in aerobic glycolysis and tumorigenesis in HCC. Here, we found that FOXP2 was lower expressed in HCC tissues and cells than in nontumor tissues and normal hepatocytes. Overexpression of FOXP2 suppressed cell proliferation and invasion of HCC cells and promoted cell apoptosis in vitro, and hindered the growth of mouse xenograft tumors in vivo. Further researches showed that FOXP2 inhibited the Warburg effect in HCC cells. Moreover, we demonstrated that FOXP2 up‐regulated the expression of fructose‐1, 6‐diphosphatase (FBP1), and the inhibitory effect of FOXP2 on glycolysis was dependent on FBP1. Mechanistically, as a transcription factor, FOXP2 negatively regulated the transcription of lysine‐specific demethylase 5A (KDM5A), and then blocked KDM5A‐induced H3K4me3 demethylation in FBP1 promoter region, thereby promoting the expression of FBP1. Consistently, overexpressing KDM5A or silencing FBP1 effectively reversed the inhibitory effect of FOXP2 on HCC progression. Together, our findings revealed the mechanistic role of the FOXP2/KDM5A/FBP1 axis in glycolysis and malignant progression of HCC cells, providing a potential molecular target for the therapy of HCC.

show abstract

“…Genome-wide associated risk loci for attention-deficit/hyperactivity disorder (ADHD) include a hit near the Forkhead box P2 (FOXP2) gene region [1]. This gene encodes a member of the forkhead/winged-helix family of transcription factors that modulates the embryonic expression of hundreds of genes involved mainly in neuronal growth, neural development, and synaptic plasticity [2][3][4]. These molecular functions take part in key mechanisms related to learning, memory, and cognitive functions, which are central processes in the pathophysiology of ADHD and several other psychiatric disorders [5,6].…”

Section: Introductionmentioning

confidence: 99%

Dissecting the cross-trait effects of the FOXP2 GWAS hit on clinical and brain phenotypes in adults with ADHD

Meyer

Silva

Bandeira

et al. 2022

Eur Arch Psychiatry Clin Neurosci

View full text Add to dashboard Cite

The Forkhead box P2 (FOXP2) encodes for a transcription factor with a broad role in embryonic development. It is especially represented among GWAS hits for neurodevelopmental disorders and related traits, including attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder, neuroticism, and risk-taking behaviors.While several functional studies are underway to understand the consequences of FOXP2 variation, this study aims to expand previous findings to clinically and genetically related phenotypes and neuroanatomical features among subjects with ADHD. The sample included 407 adults with ADHD and 463 controls. Genotyping was performed on the Infinium PsychArray-24 BeadChip, and the FOXP2 gene region was extracted. A genewide approach was adopted to evaluate the combined effects of FOXP2 variants (n=311) on ADHD status, severity, comorbidities, and personality traits. Independent risk variants presenting potential functional effects were further tested for association with cortical surface areas in a subsample of cases (n=87). The gene-wide analyses within the ADHD sample showed a significant association of the FOXP2 gene with harm avoidance (P=0.001; PFDR=0.015) and nominal associations with hyperactivity symptoms (P=0.026; PFDR=0.130) and antisocial personality disorder (P=0.026; PFDR=0.130). An insertion/deletion variant (rs79622555) located downstream of FOXP2 was associated with the three outcomes and nominally with the surface area of superior parietal and anterior cingulate cortices. Our results extend and refine previous GWAS findings pointing to a role of FOXP2 in several neurodevelopment-related phenotypes, mainly those involving underlying symptomatic domains of self-regulation and inhibitory control. Taken together, the available evidence may constitute promising insights into the puzzle of the FOXP2-related pathophysiology.

show abstract

Molecular networks of the FOXP2 transcription factor in the brain

Cited by 29 publications

References 182 publications

Single nuclei transcriptomics in human and non-human primate striatum implicates neuronal DNA damage and proinflammatory signaling in opioid use disorder

Single nuclei transcriptomics in human and non-human primate striatum implicates neuronal DNA damage and proinflammatory signaling in opioid use disorder

FOXP2 suppresses the proliferation, invasion, and aerobic glycolysis of hepatocellular carcinoma cells by regulating the KDM5A/FBP1 axis

Dissecting the cross-trait effects of the FOXP2 GWAS hit on clinical and brain phenotypes in adults with ADHD

Contact Info

Product

Resources

About