Epilepsy as a Novel Phenotype of BPTF-Related Disorders.

BACKGROUND: Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies (NEDDFL) is associated to BPTF gene haploinsufficiency. Epilepsy was not included in the initial descriptions of NEDDFL, but emerging evidence indicates that epileptic seizures occur in some affected individuals. This study aims to investigate the electroclinical epilepsy features in individuals with NEDDFL. METHODS: We enrolled individuals with BPTF-related seizures or interictal epileptiform discharges (IEDs) on electroencephalography (EEG). Demographic, clinical, genetic, raw EEG, and neuroimaging data as well as response to antiseizure medication were assessed. RESULTS: We studied 11 individuals with a null variant in BPTF, including five previously unpublished ones. Median age at last observation was 9 years (range: 4 to 43 years). Eight individuals had epilepsy, one had a single unprovoked seizure, and two showed IEDs only. Key features included (1) early childhood epilepsy onset (median 4 years, range: 10 months to 7 years), (2) well-organized EEG background (all cases) and brief bursts of spikes and slow waves (50% of individuals), and (3) developmental delay preceding seizure onset. Spectrum of epilepsy severity varied from drug-resistant epilepsy (27%) to isolated IEDs without seizures (18%). Levetiracetam was widely used and reduced seizure frequency in 67% of the cases. CONCLUSIONS: Our study provides the first characterization of BPTF-related epilepsy. Early-childhood-onset epilepsy occurs in 19% of subjects, all presenting with a well-organized EEG background associated with generalized interictal epileptiform abnormalities in half of these cases. Drug resistance is rare.

Effect of bromodomain PHD-finger transcription factor (BPTF) on trophoblast epithelial-to-mesenchymal transition.

The trophoblast epithelial-to-mesenchymal transition (EMT) is a procedure related to embryo implantation, spiral artery establishment and fetal-maternal communication, which is a key event for successful pregnancy. Inadequate EMT is one of the pathological mechanisms of recurrent miscarriage (RM). Whole-exome sequencing revealed that the mutation of bromodomain PHD-finger transcription factor (BPTF) was strongly associated with RM. In the present study, the effects of BPTF on EMT and the underlying mechanism were investigated. We found that the expression of BPTF in the villi of RM patients was significantly downregulated. Gene Ontology (GO) analysis revealed that BPTF participated in cell adhesion. The knockdown of BPTF prevented EMT and attenuated trophoblast invasion in vitro. BPTF activated Slug transcription by binding directly to the promoter region of the Slug gene. Interestingly, the protein levels of both Slug and BPTF were decreased in the villous cytotrophoblasts (VCTs) of RM villi. In conclusion, BPTF participates in the regulation of trophoblast EMT by activating Slug expression, suggesting that BPTF defects are an important factor in RM pathogenesis.

BPTF activates the MAPK pathway through coexpression with Raf1 to promote proliferation of T-cell lymphoma.

The aim of the present study was to explore the role and biological function of bromodomain PHD finger transcription factor (BPTF) in T-cell lymphoma. Reverse transcription-quantitative PCR (RT-qPCR), western blotting, immunohistochemistry and bioinformatics analysis were used to determine the expression levels of BPTF and Raf1 in T-cell lymphoma tissues and matched adjacent normal tissues. RT-qPCR and western blot analyses were used to examine the role of BPTF in the activation of MAPK signaling. The function of BPTF and Raf1 in T-cell lymphoma was investigated through in vitro and in vivo assays (MTT assay, colony formation assay, flow cytometry, western blotting, tumor xenograft model and TUNEL assay) following silencing and overexpression experiments in Hut-102 cells. The results demonstrated that BPTF and Raf1 were overexpressed in T-cell lymphoma tissues compared with normal tissues, and high expression of BPTF or Raf1 was associated with advanced clinical stage. BPTF promoted the activation of the MAPK pathway and was coexpressed with Raf1 in T-cell lymphoma tissues. Functional assays demonstrated that silencing of BPTF or Raf1 in Hut-102 cells suppressed cell proliferation and induced apoptosis. Furthermore, the carcinogenic effect of BPTF was confirmed by xenograft experiments in nude mice. The present findings suggested that BPTF may function as a crucial oncogenic factor and may serve as a novel therapeutic target in T-cell lymphoma.

Progress on the relationship between BPTF and development of tumors in children / 国际儿科学杂志

The gene of bromodomain PHD finger transcription factor (BPTF) is expressed in all tissues and its protein regulate the transcription process.Overexpression and mutations of BPTF are found in a variety of tumors,which demonstrate poor prognosis.It is also reported that BPTF plays an important role in the development of childhood malignancy.The study aims to summarize the latest studies of tumors in children associated with BPTF.

Analysis of rice Snf2 family proteins and their potential roles in epigenetic regulation.

Snf2 family proteins are ATP-dependent chromatin remodeling factors that control many aspects of DNA events such as transcription, replication, homologous recombination and DNA repair. In animals several members in this family have been revealed to control gene expression in concert with other epigenetic mechanisms including histone modification, histone variants and DNA methylation. Their function in regulating genome expression in plant has hardly been disclosed before except in Arabidopsis. Here we identified 40 members of this family in the rice (Oryza Sativa) genome and constructed a phylogenetic tree together with Arabidopsis 41 Snf2 proteins. Sequence alignment of the Snf2 helicase regions revealed conserved motifs and blocks in most proteins. Expression profile analysis indicates that many rice Snf2 family genes show a tissue-specific expression pattern and some of them respond to abiotic stresses including drought, salt and cold. The results provide a basis for further analysis of their roles in epigenetic regulation to control rice development.