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      • Arabidopsis ING and Alfin1-like protein families localize to the nucleus and bind to H3K4me3/2 via plant homeodomain fingers

        Lee, Woo Yong,Lee, Daeyoup,Chung, Won-Il,Kwon, Chang Seob Blackwell Publishing Ltd 2009 The Plant journal Vol.58 No.3

        <P>Summary</P><P>In yeast and animals, tri- and dimethylation of histone H3 at lysine 4 (H3K4me3/2) are markers of transcriptionally active genes that have recently been shown to be primary ligands for the plant homeodomain (PHD) finger. However, PHD fingers able to bind to H3K4me3/2 have not been identified in plants. Here, we identify 83 canonical PHD fingers in the Arabidopsis proteome database that are supported by both SMART and Pfam prediction. Among these, we focus on PHD fingers in ING (inhibitor of growth) homologues (AtING) and Alfin1-like (AL) proteins, which are highly similar to those in human ING2 and bromodomain PHD finger transcription factor (BPTF), based on predicted tertiary structures. ING proteins are found in yeast, animals and plants, whereas AL proteins exist only in plants. <I>In vitro</I> binding experiments indicated that PHD fingers in AtING and AL proteins in Arabidopsis can bind to H3K4me3, and, to a lesser extent, to H3K4me2. In addition, mutational analysis confirmed that a predicted aromatic cage and a specific conserved acidic residue are both crucial for binding to H3K4me3/2. Finally, we demonstrate that AtING and AL proteins are nuclear proteins that are expressed in various tissues of the Arabidopsis plant. Thus, we propose that ING and AL proteins are nuclear proteins that are involved in chromatin regulation by binding to H3K4me3/2, the active histone markers, in plants.</P>

      • DFR: an efficient directional flooding‐based routing protocol in underwater sensor networks

        Shin, Dongseung,Hwang, Daeyoup,Kim, Dongkyun Wiley Subscription Services, Inc., A Wiley Company 2012 WIRELESS COMMUNICATIONS AND MOBILE COMPUTING Vol.12 No.17

        <P><B>ABSTRACT</B></P><P>Unlike terrestrial sensor networks, underwater sensor networks (UWSNs) have salient features such as a long propagation delay, narrow bandwidth, and high packet loss over links. Hence, path setup‐based routing protocols proposed for terrestrial sensor networks are not applicable because a large latency of the path establishment is observed, and packet delivery is not reliable in UWSNs. Even though routing protocols such as VBF (vector based forwarding) and HHVBF (hop‐by‐hop VBF) were introduced for UWSNs, their performance in terms of reliability deteriorates at high packet loss. In this paper, we therefore propose a directional flooding‐based routing protocol, called DFR, in order to achieve reliable packet delivery. DFR performs a so‐called controlled flooding, where DFR changes the number of nodes which participate in forwarding a packet according to their link quality. When a forwarding node has poor link quality to its neighbor nodes geographically advancing toward the sink, DFR allows more nodes to participate in forwarding the packet. Otherwise, a few nodes are enough to forward the packet reliably. In addition, we identify two types of void problems which can occur during the controlled flooding and introduce their corresponding solutions. Our simulation study using ns‐2 simulator proves that DFR is more suitable for UWSNs, especially when links are prone to packet loss. Copyright © 2011 John Wiley & Sons, Ltd.</P>

      • KCI등재후보

        Cell line-specific features of 3D chromatin organization in hepatocellular carcinoma

        Yeonwoo Kim,Hyeokjun Yang,Daeyoup Lee Korea Genome Organization 2023 Genomics & informatics Vol.21 No.2

        Liver cancer, particularly hepatocellular carcinoma (HCC), poses a significant global threat to human lives. To advance the development of innovative diagnostic and treatment approaches, it is essential to examine the hidden features of HCC, particularly its 3D genome architecture, which is not well understood. In this study, we investigated the 3D genome organization of four HCC cell lines-Hep3B, Huh1, Huh7, and SNU449-using in situ Hi-C and assay for transposase-accessible chromatin sequencing. Our findings revealed that HCC cell lines had more long-range interactions, both intra-and interchromosomal, compared to human mammary epithelial cells (HMECs). Unexpectedly, HCC cell lines displayed cell line-specific compartmental modifications at the megabase (Mb) scale, which could potentially be leveraged in determining HCC subtypes. At the sub-Mb scale, we observed decreases in intra-TAD (topologically associated domain) interactions and chromatin loops in HCC cell lines compared to HMECs. Lastly, we discovered a correlation between gene expression and the 3D chromatin architecture of SLC8A1, which encodes a sodium-calcium antiporter whose modulation is known to induce apoptosis by comparison between HCC cell lines and HMECs. Our findings suggest that HCC cell lines have a distinct 3D genome organization that is different from those of normal and other cancer cells based on the analysis of compartments, TADs, and chromatin loops. Overall, we take this as evidence that genome organization plays a crucial role in cancer phenotype determination. Further exploration of epigenetics in HCC will help us to better understand specific gene regulation mechanisms and uncover novel targets for cancer treatment.

      • Histone occupancy-dependent and -independent removal of H3K27 trimethylation at cold-responsive genes in Arabidopsis

        Kwon, Chang Seob,Lee, Daeyoup,Choi, Giltsu,Chung, Won-Il Blackwell Publishing Ltd 2009 The Plant journal Vol.60 No.1

        <P>Summary</P><P>Trimethylation of histone H3 at lysine 27 (H3K27me3) is a histone marker that is present in inactive gene loci in both plants and animals. Transcription of some of the genes with H3K27me3 should be induced by internal or external cues, yet the dynamic fate of H3K27me3 in these genes during transcriptional regulation is poorly understood in plants. Here we show that H3K27me3 in two cold-responsive genes, <I>COR15A</I> and <I>ATGOLS3</I>, decreases gradually in Arabidopsis during exposure to cold temperatures. We found that removal of H3K27me3 can occur by both histone occupancy-dependent and -independent mechanisms. Upon cold exposure, histone H3 levels decreased in the promoter regions of <I>COR15A</I> and <I>ATGOLS3</I> but not in their transcribed regions. When we returned cold-exposed plants to normal growth conditions, transcription of <I>COR15A</I> and <I>ATGOLS3</I> was completely repressed to the initial level before cold exposure in 1 day. In contrast, plants still maintained the cold-triggered decrease in H3K27me3 at <I>COR15A</I> and <I>ATGOLS3</I>, but this decrease did not enhance transcriptional induction of the two genes upon re-exposure to cold. Taken together, these results indicate that gene activation is not inhibited by H3K27me3 itself but rather leads to removal of H3K27me3, and that H3K27me3 can be inherited at a quantitative level, thereby serving as a memory marker for recent transcriptional activity in Arabidopsis.</P>

      • SCISCIESCOPUS

        Decoding the genome with an integrative analysis tool: Combinatorial CRM Decoder

        Kang, Keunsoo,Kim, Joomyeong,Chung, Jae Hoon,Lee, Daeyoup Oxford University Press 2011 Nucleic acids research Vol.39 No.17

        <P>The identification of genome-wide <I>cis</I>-regulatory modules (CRMs) and characterization of their associated epigenetic features are fundamental steps toward the understanding of gene regulatory networks. Although integrative analysis of available genome-wide information can provide new biological insights, the lack of novel methodologies has become a major bottleneck. Here, we present a comprehensive analysis tool called combinatorial CRM decoder (CCD), which utilizes the publicly available information to identify and characterize genome-wide CRMs in a species of interest. CCD first defines a set of the epigenetic features which is significantly associated with a set of known CRMs as a code called ‘trace code’, and subsequently uses the trace code to pinpoint putative CRMs throughout the genome. Using 61 genome-wide data sets obtained from 17 independent mouse studies, CCD successfully catalogued ∼12 600 CRMs (five distinct classes) including polycomb repressive complex 2 target sites as well as imprinting control regions. Interestingly, we discovered that ∼4% of the identified CRMs belong to at least two different classes named ‘multi-functional CRM’, suggesting their functional importance for regulating spatiotemporal gene expression. From these examples, we show that CCD can be applied to any potential genome-wide datasets and therefore will shed light on unveiling genome-wide CRMs in various species.</P>

      • SCISCIESCOPUS

        Octopus-toolkit: a workflow to automate mining of public epigenomic and transcriptomic next-generation sequencing data

        Kim, Taemook,Seo, Hogyu David,Hennighausen, Lothar,Lee, Daeyoup,Kang, Keunsoo Oxford University Press 2018 Nucleic acids research Vol.46 No.9

        <P><B>Abstract</B></P><P>Octopus-toolkit is a stand-alone application for retrieving and processing large sets of next-generation sequencing (NGS) data with a single step. Octopus-toolkit is an automated set-up-and-analysis pipeline utilizing the Aspera, SRA Toolkit, FastQC, Trimmomatic, HISAT2, STAR, Samtools, and HOMER applications. All the applications are installed on the user's computer when the program starts. Upon the installation, it can automatically retrieve original files of various epigenomic and transcriptomic data sets, including ChIP-seq, ATAC-seq, DNase-seq, MeDIP-seq, MNase-seq and RNA-seq, from the gene expression omnibus data repository. The downloaded files can then be sequentially processed to generate BAM and BigWig files, which are used for advanced analyses and visualization. Currently, it can process NGS data from popular model genomes such as, human (<I>Homo sapiens</I>), mouse (<I>Mus musculus</I>), dog (<I>Canis lupus familiaris</I>), plant (<I>Arabidopsis thaliana</I>), zebrafish (<I>Danio rerio</I>), fruit fly (<I>Drosophila melanogaster</I>), worm (<I>Caenorhabditis elegans</I>), and budding yeast (<I>Saccharomyces cerevisiae</I>) genomes. With the processed files from Octopus-toolkit, the meta-analysis of various data sets, motif searches for DNA-binding proteins, and the identification of differentially expressed genes and/or protein-binding sites can be easily conducted with few commands by users. Overall, Octopus-toolkit facilitates the systematic and integrative analysis of available epigenomic and transcriptomic NGS big data.</P>

      • Chd1p recognizes H3K36Ac to maintain nucleosome positioning near the transcription start site

        Kim, Hyunhee,Jo, Hyelim,Seo, Hogyu David,Park, Hee-Sung,Lee, Daeyoup Elsevier 2018 Biochemical and biophysical research communication Vol.503 No.3

        <P><B>Abstract</B></P> <P>In <I>Saccharomyces cerevisiae</I>, the ATP-dependent chromatin remodeler, Chd1p, globally affects nucleosome positioning at coding regions, where nucleosomes are specifically and directionally aligned with respect to the transcription start site (TSS). Various auxiliary domains of remodelers play critical roles by performing specialized functions that are unique to the type of remodeler. Here, we report that yeast Chd1p directly binds to acetylated histone H3K36 (H3K36Ac) via its chromodomain, and that H3K36Ac stimulates the nucleosome sliding activity of Chd1p <I>in vitro</I>. Furthermore, we use genome-wide analysis to demonstrate that H3K36Ac promotes the remodeling activity of Chd1p to maintain chromatin stability at the 5′ ends of genes <I>in vivo</I>. Our work linking Chd1p with H3K36Ac provides novel insights into how the nucleosome remodeling activity of Chd1p is controlled near the TSS.</P>

      • Biogenesis and regulation of the <i>let-7</i> miRNAs and their functional implications

        Lee, Hosuk,Han, Sungwook,Kwon, Chang Seob,Lee, Daeyoup Higher Education Press 2016 Protein & cell Vol.7 No.2

        <P>The <I>let-7</I> miRNA was one of the first miRNAs discovered in the nematode, <I>Caenorhabditis elegans</I>, and its biological functions show a high level of evolutionary conservation from the nematode to the human. Unlike in <I>C. elegans</I>, higher animals have multiple isoforms of <I>let-7</I> miRNAs; these isoforms share a consensus sequence called the ‘seed sequence’ and these isoforms are categorized into <I>let-7</I> miRNA family. The expression of <I>let-7</I> family is required for developmental timing and tumor suppressor function, but must be suppressed for the self-renewal of stem cells. Therefore, <I>let-7</I> miRNA biogenesis must be carefully controlled. To generate a <I>let-7</I> miRNA, a primary transcript is produced by RNA polymerase II and then subsequently processed by Drosha/DGCR8, TUTase, and Dicer. Because dysregulation of <I>let-7</I> processing is deleterious, biogenesis of <I>let-7</I> is tightly regulated by cellular factors, such as the RNA binding proteins, LIN28A/B and DIS3L2. In this review, we discuss the biological functions and biogenesis of <I>let-7</I> miRNAs, focusing on the molecular mechanisms of regulation of <I>let-7</I> biogenesis in vertebrates, such as the mouse and the human.</P>

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