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Age-related epigenetic regulation in the brain and its role in neuronal diseases
( Jeongsil Kim-ha ),( Young-joon Kim ) 생화학분자생물학회(구 한국생화학분자생물학회) 2016 BMB Reports Vol.49 No.12
Accumulating evidence indicates many brain functions are mediated by epigenetic regulation of neural genes, and their dysregulations result in neuronal disorders. Experiences such as learning and recall, as well as physical exercise, induce neuronal activation through epigenetic modifications and by changing the noncoding RNA profiles. Animal models, brain samples from patients, and the development of diverse analytical methods have broadened our understanding of epigenetic regulation in the brain. Diverse and specific epigenetic changes are suggested to correlate with neuronal development, learning and memory, aging and age-related neuronal diseases. Although the results show some discrepancies, a careful comparison of the data (including methods, regions and conditions examined) would clarify the problems confronted in understanding epigenetic regulation in the brain. [BMB Reports 2016; 49(12): 671-680]
Kim, Taeil,Yoon, Joonsun,Cho, Hwansung,Lee, Wook-bin,Kim, Joon,Song, Young-Hwa,Kim, Se Nyun,Yoon, Jeong Ho,Kim-Ha, Jeongsil,Kim, Young-Joon Nature America Inc 2005 Nature immunology Vol.6 No.2
IκB kinase (IKK) and Jun N-terminal kinase (Jnk) signaling modules are important in the synthesis of immune effector molecules during innate immune responses against lipopolysaccharide and peptidoglycan. However, the regulatory mechanisms required for specificity and termination of these immune responses are unclear. We show here that crosstalk occurred between the drosophila Jnk and IKK pathways, which led to downregulation of each other's activity. The inhibitory action of Jnk was mediated by binding of drosophila activator protein 1 (AP1) to promoters activated by the transcription factor NF-κB. This binding led to recruitment of the histone deacetylase dHDAC1 to the promoter of the gene encoding the antibacterial protein Attacin-A and to local modification of histone acetylation content. Thus, AP1 acts as a repressor by recruiting the deacetylase complex to terminate activation of a group of NF-κB target genes.
Precocious Expression of Drosophila Rbp9 Inhibits Ovarian Germ Cell Proliferation
Jeongsil Kim-Ha,Kyoungsuk Jeong 한국분자세포생물학회 2004 Molecules and cells Vol.18 No.2
We previously reported that Rbp9 is expressed in the germarium region as soon as germ cells complete mitosis and form 16 interconnected cystocytes. Mutation of Rbp9 caused over-proliferation of cystocytes and generated an ovarian tumor phenotype. This led us to conclude that Rbp9 either inhibits cell proliferation or is required for cell differentiation. To examine the role of Rbp9, we over-expressed it ectopically in germline stem cells and early stage cystocytes that had not yet formed 16 cell clusters. The egg chambers of the newly eclosed transgenic flies looked normal. However, on day 12, most of the developing egg chambers had disappeared and only the germarium region remained. Staining of the Rbp9 over-expressing transgenic ovaries with mitosis markers revealed almost no mitotic divisions in the transgenic germaria. Further examination of these cystocytes with HTS [hu-li tai shao protein], which labels the fusome structure, revealed that the cells in the germarium region consisted of stem cells and cystocytes that had not yet completed four mitotic divisions. These observations suggest that precocious expression of Rbp9 inhibits cystocyte proliferation. Therefore the precise onset of Rbp9 expression in germarium region 2a is critical for inhibiting their further proliferation and achieving their correct differentiation.
Blood-Brain Barrier Defects Associated with Rbp9 Mutation
Jihyun Kim,Young-Joon Kim,Jeongsil Kim-Ha 한국분자세포생물학회 2010 Molecules and cells Vol.29 No.1
Rbp9 is a Drosophila RNA-binding protein that shares a high level of sequence similarity with Drosophila elav and human Hu proteins. Loss of function alleles of elav are embryonic lethal causing abnormal central nervous sys-tem (CNS) development, and Hu is implicated in the devel-opment of paraneoplastic neurological syndrome associ-ated with small cell lung cancer. To elucidate the role of Rbp9, we generated Rbp9 mutant flies and examined them for symptoms related to paraneoplastic encephalomyelitis. Although Rbp9 proteins begin to appear from the middle of the pupal period in the cortex of the CNS, the Rbp9 mu-tants showed no apparent defects in development. How-ever, as the mutant adult flies grew older, they showed reduced locomotor activities and lived only one-half of the life expectancy of wild-type flies. To understand the mo-lecular mechanism underlying this symptom, gene ex-pression profiles in Rbp9 mutants were analyzed and po-tential target genes were further characterized. Reduced expression of cell adhesion molecules was detected, and defects in the blood-brain barrier (BBB) of Rbp9 mutant brains could be seen. Putative Rbp9-binding sites were found in introns of genes that function in cell adhesion. Therefore, Rbp9 may regulate the splicing of cell adhesion molecules, critical for the formation of the BBB.
( Si-cho Kim ),( Jiwon Kim ),( Da-won Kim ),( Yanghee Choi ),( Kyunghyun Park ),( Eun Ju Cho ),( Su Jong Yu ),( Jeongsil Kim-ha ),( Young-joon Kim ) 생화학분자생물학회 2022 BMB Reports Vol.55 No.11
Hepatocellular carcinoma (HCC) is dangerous cancer that often evades early detection because it is asymptomatic and an effective detection method is lacking. For people with chronic liver inflammation who are at high risk of developing HCC, a sensitive detection method for HCC is needed. In a meta-analysis of The Cancer Genome Atlas pan-cancer methylation database, we identified a CpG island in the USP44 promoter that is methylated specifically in HCC. We developed methylation-sensitive high-resolution melting (MS-HRM) analysis to measure the methylation levels of the USP promoter in cell-free DNA isolated from patients. Our MS-HRM assay correctly identified 40% of patients with early-stage HCC, whereas theα-fetoprotein test, which is currently used to detect HCC, correctly identified only 25% of early-stage HCC patients. These results demonstrate that USP44 MS-HRM analysis is suitable for HCC surveillance. [BMB Reports 2022; 55(11): 553-558]
Jin, Li Hua,Choi, Jung Kyoon,Kim, Byungil,Cho, Hwan Sung,Kim, Jihyun,Kim-Ha, Jeongsil,Kim, Young-Joon American Society for Microbiology 2009 Molecular and cellular biology Vol.29 No.6
<B>ABSTRACT</B><P><I>Drosophila</I> producing a mutant form of the putative transcription coregulator, Split ends (Spen), originally identified in the analysis of neuronal development, display diverse immune defects. In order to understand the role of Spen in the innate immune response, we analyzed the transcriptional defects associated with <I>spen</I> mutant hemocytes and their relationship to the Notch signaling pathways. Spen is regulated by the Notch pathway in the lymph glands and is required for Notch-dependent activation of a large number of genes involved in energy metabolism and differentiation. Analysis of the epigenetic marks associated with Spen-dependent genes indicates that Spen performs its function as a coactivator by regulating chromatin modification. Intriguingly, expression of the Spen-dependent genes was transiently downregulated in a Notch-dependent manner by the Dif activated upon recognition of pathogen-associated molecules, demonstrating the existence of cross talk between hematopoietic regulation and the innate immune response. Our observations reveal a novel connection between the Notch and Toll/IMD signaling pathways and demonstrate a coactivating role for Spen in activating Notch-dependent genes in differentiating cells.</P>
Jihyun Kim,Nuri Choi,Jeongsil Kim-Ha 생화학분자생물학회 2023 BMB Reports Vol.56 No.4
Glial cells play important roles during neurogenesis and inmaintaining complex functions of the nervous system. Here,we report the characterization of a gene, Sdr, which contains aputative insulin-like growth factor receptor domain and is requiredto maintain critical nervous system functions in Drosophila. Sdr is expressed in glial cells during embryonic and larval stagesof development, but its role in adult flies is poorly understood. As insulin signaling is important throughout the lifespan inhuman, we investigated the Sdr’s role in adult flies. Our resultsdemonstrate that Sdr is expressed on surface glial cells thatsurround the nervous system. Mutation of Sdr did not affect developmentbut caused defects in locomotion and lifespan. Sdrmutants also showed increasingly severe defects in the bloodbrain-and blood-retina-barriers as they aged. Therefore, wesuggest a novel role of Sdr in maintaining the integrity of theblood-brain- and blood-retina-barriers in adult flies.