Identifying key genes in COPD risk via multiple population data integration and gene prioritization.

Chronic obstructive pulmonary disease (COPD) is a highly prevalent disease, making it a leading cause of death worldwide. Several genome-wide association studies (GWAS) have been conducted to identify loci associated with COPD. However, different ancestral genetic compositions for the same disease across various populations present challenges in studies involving multi-population data.

PNPO-PLP axis senses prolonged hypoxia in macrophages by regulating lysosomal activity.

Oxygen is critical for all metazoan organisms on the earth and impacts various biological processes in physiological and pathological conditions. While oxygen-sensing systems inducing acute hypoxic responses, including the hypoxia-inducible factor pathway, have been identified, those operating in prolonged hypoxia remain to be elucidated. Here we show that pyridoxine 5'-phosphate oxidase (PNPO), which catalyses bioactivation of vitamin B6, serves as an oxygen sensor and regulates lysosomal activity in macrophages.

C4S DB: Comprehensive Collection and Comparison for ChIP-Seq Database.

Combining multiple binding profiles, such as transcription factors and histone modifications, is a crucial step in revealing the functions of complex biological systems. Although a massive amount of chromatin immunoprecipitation followed by sequencing (ChIP-seq) data is available, existing ChIP-seq databases or repositories focus on individual experiments, and it is difficult to elucidate orchestrated regulation by DNA-binding elements. We developed the Comprehensive Collection and Comparison for ChIP-Seq Database (C4S DB) to provide researchers with insights into the combination of DNA binding elements based on quality-assessed public ChIP-seq data.

Deficiency of , a gene related to intellectual disability, causes impaired neuronal development and a mild behavioural phenotype.

is a gene associated with intellectual disability, which was originally identified as being involved in the maintenance of kinetochore-microtubule attachment. To explore the neuronal defects caused by deficiency, we established mice that lack . Mice that are homozygous knockout for were slightly smaller than wild-type mice and died soon after birth on pure C57BL/6J background.

High levels of chromosomal instability facilitate the tumor growth and sphere formation.

Most cancer cells show chromosomal instability (CIN), a condition in which chromosome missegregation occurs at high rates. Growing evidence suggests that CIN is not just a consequence of, but a driving force for, oncogenic transformation, although the relationship between CIN and tumorigenesis has not been fully elucidated. Here we found that conventional two-dimensional (2D) culture of HeLa cells, a cervical cancer-derived cell line, was a heterogenous population containing cells with different CIN levels.

CEBPB is required for NRF2-mediated drug resistance in NRF2-activated non-small cell lung cancer cells.

NRF2 is a transcription activator that plays a key role in cytoprotection against oxidative stress. Although increased NRF2 activity is principally beneficial for our health, NRF2 activation in cancer cells is detrimental, as it drives their malignant progression. We previously found that CCAAT/enhancer-binding protein B (CEBPB) cooperates with NRF2 in NRF2-activated lung cancer and enhances tumour-initiating activity by promoting NOTCH3 expression.

Enhancer remodeling promotes tumor-initiating activity in NRF2-activated non-small cell lung cancers.

Transcriptional dysregulation, which can be caused by genetic and epigenetic alterations, is a fundamental feature of many cancers. A key cytoprotective transcriptional activator, NRF2, is often aberrantly activated in non-small cell lung cancers (NSCLCs) and supports both aggressive tumorigenesis and therapeutic resistance. Herein, we find that persistently activated NRF2 in NSCLCs generates enhancers at gene loci that are not normally regulated by transiently activated NRF2 under physiological conditions.

Landscape of electrophilic and inflammatory stress-mediated gene regulation in human lymphoblastoid cell lines.

Human lymphoblastoid cell lines (LCLs) are valuable for the functional analyses of diseases. We have established more than 4200 LCLs as one of the resources of an integrated biobank. While oxidative and inflammatory stresses play critical roles in the onset and progression of various diseases, the responsiveness of LCLs, especially that of biobank-made LCLs, to these stresses has not been established.

Theoretical characterisation of strand cross-correlation in ChIP-seq.

Background: Strand cross-correlation profiles are used for both peak calling pre-analysis and quality control (QC) in chromatin immunoprecipitation followed by sequencing (ChIP-seq) analysis. Despite its potential for robust and accurate assessments of signal-to-noise ratio (S/N) because of its peak calling independence, it remains unclear what aspects of quality such strand cross-correlation profiles actually measure.

Results: We introduced a simple model to simulate the mapped read-density of ChIP-seq and then derived the theoretical maximum and minimum of cross-correlation coefficients between strands.