Biology subjects

Lee, K.-H.

Publications and source records attributed to Lee, K.-H..

3 recordsLinked to original sources

bioRxiv2019

variant2literature: full text literature search for genetic variants

MotivationWhole genome sequencing (WGS) by next-generation sequencing produces millions of variants for an individual. The retrieval of biomedical literature for such a large number of genetic variants remains challenging, because in many cases the variants are only present in tables as images, or in the supplementary documents of which the file formats are diverse.\n\nResultsThe proposed tool named variant2literature from the TaiGenomics (Toolkits for AI genomics) resolves the problem by incorporating text recognition with image processing. In addition to the adoption of advanced image-based text retrieval, the recall rate of finding the literature containing the variants of interest is further improved by employing the skill of variant normalization. Different variant presentations are transformed into chromosome coordinates (standard VCF format) such that false negatives can be largely avoided. variant2literature is available in two ways. First, a web-based interface is provided to search all the literature in PMC Open Access Subset. Second, the command-line executable can be downloaded such that the users are free to search all the files in a specified directory locally.\n\nAvailabilityhttp://variant2literature.taigenomics.com/\n\nContactchienyuchen@ntu.edu.tw

genetics↗

bioRxiv2019

Physicochemical Properties of Chromosomes in Live Cells Characterized by Label-Free Imaging and Fluorescence Correlation Spectroscopy

The cell nucleus is a three-dimensional, dynamic organelle that is organized into many subnuclear bodies, such as chromatin and nucleoli. The structure and function of these bodies is maintained by diffusion and interactions between related factors as well as dynamic and structural changes. Recent studies using fluorescent microscopic techniques suggest that protein factors can access and are freely mobile in mitotic chromosomes, despite their densely packed structure. However, the physicochemical properties of the chromosome itself during cell division are not yet fully understood. Physical parameters, such as the refractive index (RI), volume of the mitotic chromosome, and diffusion coefficients of fluorescent probes inside the chromosome were quantified using an approach combining label-free optical diffraction tomography with complementary confocal laser scanning microscopy and fluorescence correlation spectroscopy. Variance in these parameters correlated among various osmotic conditions, suggesting that changes in RI are consistent with those in the diffusion coefficient for mitotic chromosomes and cytosol. Serial RI tomography images of chromosomes in live cells during mitosis were compared with three-dimensional confocal micrographs to demonstrate that compaction and decompaction of chromosomes induced by osmotic change were characterized by linked changes in chromosome RI, volume, and the mobility of fluorescent proteins.

biophysics↗

bioRxiv2018

Transcriptional activation of DBP by hnRNP K facilitates circadian rhythm.

D-site albumin promoter binding protein (DBP) supports the rhythmic transcription of downstream genes, in part by displaying high-amplitude cycling of its own transcripts compared to other circadian clock genes. However, the underlying mechanism remains elusive. Here, we demonstrated that poly(C) motif within DBP proximal promoters, in addition to an E-box element, provoked the transcriptional activation through increased RNA polymerase 2 (Pol2) recruitment by inducing higher chromatin accessibility. We also clarified that heterogeneous nuclear ribonucleoprotein K (hnRNP K) is a key regulator that binds to the poly(C) motif on single-stranded DNAs in vitro. Chromatin immunoprecipitation further confirmed the expression-dependent and rhythmic binding of hnRNP K which was inhibited through its cytosolic localization mediated by time-dependent ERK activation. Knockdown of hnRNP K triggered low-amplitude mRNA rhythms in DBP and other core clock genes through transcriptional or post-transcriptional regulation. Finally, transgenic depletion of a Drosophila homolog of hnRNP K in circadian pacemaker neurons lengthened 24-hour periodicity in free-running locomotor behaviors. Taken together, our results provide new insights into the function of hnRNP K as a transcriptional amplifier of DBP, which acts rhythmically through its intracellular localization by the ERK phosphorylation and as an mRNA stabilizer along with its physiological significance in circadian rhythms of Drosophila.\n\nSignificance StatementIn the case of mood disorders and the aging process, the mRNA expression and amplitude level of clock genes, including DBP, were reported to be diminished. However, the reason behind this decrease of clock gene amplitude and expression level remained unclear. Through this study, we revealed the regulatory mechanism behind the expression of clock genes, especially of DBP mRNA expression. In addition, we discovered that hnRNP K regulates more core clock genes than what we have previously known, such as Clock and Periods. Finally, we demonstrated the physiological significance of hnRNP K in Drosophila through its RNAi line model. Hence, our findings show the regulatory mechanism of circadian rhythm that may provide insight on mood disorder and aging process.

neuroscience↗