Chromatin gene-gene loops support the cross-regulation of genes with related function.

Chromatin loops between gene pairs have been observed in diverse contexts in both flies and vertebrates. Combining high-resolution Capture-C, DNA fluorescence in situ hybridization, and genetic perturbations, we dissect the functional role of three loops between genes with related function during Drosophila embryogenesis. By mutating the loop anchor (but not the gene) or the gene (but not loop anchor), we disentangle loop formation and gene expression and show that the 3D proximity of paralogous gene loci supports their co-regulation.

Characterization of Button Loci that Promote Homologous Chromosome Pairing and Cell-Type-Specific Interchromosomal Gene Regulation.

Homologous chromosomes colocalize to regulate gene expression in processes including genomic imprinting, X-inactivation, and transvection. In Drosophila, homologous chromosomes pair throughout development, promoting transvection. The "button" model of pairing proposes that specific regions along chromosomes pair with high affinity.

First identification of mutation in heritable pulmonary arterial hypertension.

Heritable pulmonary arterial hypertension (HPAH) is an autosomal dominantly inherited disease caused by mutations in the () gene and/or genes of its signalling pathway in approximately 85% of patients. We clinically and genetically analysed an HPAH family without mutations in previously described pulmonary arterial hypertension (PAH) genes. Clinical assessment included electrocardiogram, lung function, blood gas analysis, chest X-ray, laboratory testing, echocardiography and right heart catheterization in case of suspected disease.

Identification of genetic defects in pulmonary arterial hypertension by a new gene panel diagnostic tool.

In the present study we developed a new specific gene panel for pulmonary arterial hypertension (PAH) including major disease genes and further candidates. We assessed 37 patients with invasively confirmed PAH and five relatives of affected patients for genetic testing. A new PAH-specific gene panel was designed using next generation sequencing (NGS) including 12 known disease genes and 17 further candidates.

Pulmonary Arterial Hypertension: A Current Perspective on Established and Emerging Molecular Genetic Defects.

Pulmonary arterial hypertension (PAH) is an often fatal disorder resulting from several causes including heterogeneous genetic defects. While mutations in the bone morphogenetic protein receptor type II (BMPR2) gene are the single most common causal factor for hereditary cases, pathogenic mutations have been observed in approximately 25% of idiopathic PAH patients without a prior family history of disease. Additional defects of the transforming growth factor beta pathway have been implicated in disease pathogenesis.

Mutation in BMPR2 Promoter: A 'Second Hit' for Manifestation of Pulmonary Arterial Hypertension?

Background: Hereditary pulmonary arterial hypertension (HPAH) can be caused by autosomal dominant inherited mutations of TGF-β genes, such as the bone morphogenetic protein receptor 2 (BMPR2) and Endoglin (ENG) gene. Additional modifier genes may play a role in disease manifestation and severity. In this study we prospectively assessed two families with known BMPR2 or ENG mutations clinically and genetically and screened for a second mutation in the BMPR2 promoter region.

Comprehensive expression map of transcription regulators in the adult zebrafish telencephalon reveals distinct neurogenic niches.

The zebrafish has become a model to study adult vertebrate neurogenesis. In particular, the adult telencephalon has been an intensely studied structure in the zebrafish brain. Differential expression of transcriptional regulators (TRs) is a key feature of development and tissue homeostasis.

The helix-loop-helix protein id1 controls stem cell proliferation during regenerative neurogenesis in the adult zebrafish telencephalon.

The teleost brain has the remarkable ability to generate new neurons and to repair injuries during adult life stages. Maintaining life-long neurogenesis requires careful management of neural stem cell pools. In a genome-wide expression screen for transcription regulators, the id1 gene, encoding a negative regulator of E-proteins, was found to be upregulated in response to injury.