• BMB Reports
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• 제56권2호
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• pp.108-113
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• 2023

Cohesin is a ring-shaped protein complex that comprises the SMC1, SMC3, and α-kleisin proteins, STAG1/2/3 subunits, and auxiliary factors. Cohesin participates in chromatin remodeling, chromosome segregation, DNA replication, and gene expression regulation during the cell cycle. Mitosis-specific α-kleisin factor RAD21 and meiosis-specific α-kleisin factor REC8 are expressed in embryonic stem cells (ESCs) to maintain pluripotency. Here, we demonstrated that RAD21 and REC8 were involved in maintaining genomic stability and modulating chromatin modification in murine ESCs. When the kleisin subunits were depleted, DNA repair genes were downregulated, thereby reducing cell viability and causing replication protein A (RPA) accumulation. This finding suggested that the repair of exposed single-stranded DNA was inefficient. Furthermore, the depletion of kleisin subunits induced DNA hypermethylation by upregulating DNA methylation proteins. Thus, we proposed that the cohesin complex plays two distinct roles in chromatin remodeling and genomic integrity to ensure the maintenance of pluripotency in ESCs.

• 한국잠사학회:학술대회논문집
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• 한국잠사학회 2003년도 International Symposium of Silkworm/Insect Biotechnology and Annual Meeting of Korea Society of Sericultural Science
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• pp.19-22
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• 2003

Chromatin structure plays a critical role in the regulation of transcription. Drosophila GAGA factor directs chromatin remodeling to its binding sites. We found that Drosaphiia FACT, a heterodimer of dSPT16 and dSSRPl, is associated with GAGA factor through its dSSRPl subunit, binds to a nucleosome and facilitates GAGA factor-directed chromatin remodeling. Immunostaining of polytene chromosomes revealed colocalization of GAGA factor and FACT in many specific loci. (omitted)

• Molecules and Cells
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• 제20권2호
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• pp.183-188
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• 2005

INI1/hSNF5/BAF47 is a core component of the hSWI/ SNF ATP-dependent chromatin remodeling complex, and it has been implicated in regulating gene expression, cell division and tumorigenesis. We investigated whether INI1/hSNF5/BAF47 functions in activation of the colony stimulating factor 1 (CSF1) promoter in HeLa cells. Overexpression of INI1/hSNF5/BAF47 promoted CSF1 transcription, and siRNA targeting INI1/hSNF5/ BAF47 (siINI1) strongly inhibited the activity of the CSF1 promoter. We demonstrated that all conserved domains of INI1/hSNF5/BAF47 are needed for CSF1 transcription. ChIP experiment showed that INI1/ hSNF5/BAF47 is recruited to the region of the CSF1 promoter. Taken together, these results indicate that INI1/hSNF5/BAF47 is involved in activation of the CSF1 promoter.

• 생물정신의학
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• 제15권4호
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• pp.243-253
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• 2008

In the post-genomic era, the mechanisms controlling activation of genes are thought to be more important. Gene-environment interactions are crucial in both development and treatment of psychiatric disorders as they are complex genetic disorders. Epigenetics is defined as a change of gene expression that occurs without a change of DNA sequence and can be heritable by certain mechanisms. Epigenetic changes play essential roles in control of gene activation. DNA methylation, chromatin remodeling and RNAi act as key mechanisms for epigenetic modifications of genes. Here, we review the basic mechanisms of epigenetics and discuss their potential involvement of human diseases, including psychiatric disorders.

• BMB Reports
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• 제52권4호
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• pp.227-238
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• 2019

GROWTH-REGULATING FACTORs (GRFs) are sequence-specific DNA-binding transcription factors that regulate various aspects of plant growth and development. GRF proteins interact with a transcription cofactor, GRF-INTERACTING FACTOR (GIF), to form a functional transcriptional complex. For its activities, the GRF-GIF duo requires the SWITCH2/SUCROSE NONFERMENTING2 chromatin remodeling complex. One of the most conspicuous roles of the duo is conferring the meristematic potential on the proliferative and formative cells during organogenesis. GRF expression is post-transcriptionally down-regulated by microRNA396 (miR396), thus constructing the GRF-GIF-miR396 module and fine-tuning the duo's action. Since the last comprehensive review articles were published over three years ago, many studies have added further insight into its action and elucidated new biological roles. The current review highlights recent advances in our understanding of how the GRF-GIF-miR396 module regulates plant growth and development. In addition, I revise the previous view on the evolutionary origin of the GRF gene family.

• Molecules and Cells
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• 제44권2호
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• pp.101-115
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• 2021

The INO80 chromatin remodeling complex has roles in many essential cellular processes, including DNA replication. However, the mechanisms that regulate INO80 in these processes remain largely unknown. We previously reported that the stability of Ino80, the catalytic ATPase subunit of INO80, is regulated by the ubiquitin proteasome system and that BRCA1-associated protein-1 (BAP1), a nuclear deubiquitinase with tumor suppressor activity, stabilizes Ino80 via deubiquitination and promotes replication fork progression. However, the E3 ubiquitin ligase that targets Ino80 for proteasomal degradation was unknown. Here, we identified the C-terminus of Hsp70-interacting protein (CHIP), the E3 ubiquitin ligase that functions in cooperation with Hsp70, as an Ino80-interacting protein. CHIP polyubiquitinates Ino80 in a manner dependent on Hsp70. Contrary to our expectation that CHIP degrades Ino80, CHIP instead stabilizes Ino80 by extending its half-life. The data suggest that CHIP stabilizes Ino80 by inhibiting degradative ubiquitination. We also show that CHIP works together with BAP1 to enhance the stabilization of Ino80, leading to its chromatin binding. Interestingly, both depletion and overexpression of CHIP compromise replication fork progression with little effect on fork stalling, as similarly observed for BAP1 and Ino80, indicating that an optimal cellular level of Ino80 is important for replication fork speed but not for replication stress suppression. This work therefore idenitifes CHIP as an E3 ubiquitin ligase that stabilizes Ino80 via nondegradative ubiquitination and suggests that CHIP and BAP1 act in concert to regulate Ino80 ubiquitination to fine-tune its stability for efficient DNA replication.

• Journal of Korean Neurosurgical Society
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• 제61권3호
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• pp.302-311
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• 2018

Atypical teratoid rhabdoid tumours (ATRTs) are the most common malignant central nervous system tumours in children ${\leq}1year$ of age and represent approximately 1-2% of all pediatric brain tumours. ATRT is a primarily monogenic disease characterized by the bi-allelic loss of the SMARCB1 gene, which encodes the hSNF5 subunit of the SWI/SNF chromatin remodeling complex. Though conventional dose chemotherapy is not effective in most ATRT patients, high dose chemotherapy with autologous stem cell transplant, radiotherapy and/or intrathecal chemotherapy all show significant potential to improve patient survival. Recent epigenetic and transcriptional studies highlight three subgroups of ATRT, each with distinct clinical and molecular characteristics with corresponding therapeutic sensitivities, including epigenetic targeting, and inhibition of tyrosine kinases or growth/lineage specific pathways.

• 한국자기공명학회논문지
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• 제13권1호
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• pp.56-63
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• 2009

SWIRM domain, a core domain of SRG3 is well conserved in SW13, RSC8, and MOIRA family proteins. To understand structural basis for cellular functions of the SWIRM domain, we have initiated biochemical and structural studies on SWIRM domain and mutants using gelfiltration chromatography, circular dichroism and NMR spectroscopy. The structural properties of the mutant SWIRM domains (K34A and M75A) have been characterized, showing that the structures of both wild-type and mutant proteins are a-helical conformation. The data conclude that mutations at interaction sites of its binding partner protein do not affect its secondary and tertiary structure.

• Molecules and Cells
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• 제41권4호
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• pp.362-372
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• 2018

High mobility group box 2 (HMGB2) is an abundant, chromatin-associated, non-histone protein involved in transcription, chromatin remodeling, and recombination. Recently, the HMGB2 gene was found to be significantly downregulated during senescence and shown to regulate the expression of senescent-associated secretory proteins. Here, we demonstrate that HMGB2 transcription is repressed by p21 during radiation-induced senescence through the ATM-p53-p21 DNA damage signaling cascade. The loss of p21 abolished the downregulation of HMGB2 caused by ionizing radiation, and the conditional induction of p21 was sufficient to repress the transcription of HMGB2. We also showed that the p21 protein binds to the HMGB2 promoter region, leading to sequestration of RNA polymerase and transcription factors E2F1, Sp1, and p300. In contrast, NF-Y, a CCAAT box-binding protein complex, is required for the expression of HMGB2, but NF-Y binding to the HMGB2 promoter was unaffected by either radiation or p21 induction. A proximity ligation assay results confirmed that the chromosome binding of E2F1 and Sp1 was inhibited by p21 induction. As HMGB2 have been shown to regulate premature senescence by IR, targeting the p21-mediated repression of HMGB2 could be a strategy to overcome the detrimental effects of radiation-induced senescence.

• 미생물학회지
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• 제53권1호
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• pp.49-54
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• 2017

Sus1 / ENY2는 진핵생물에 잘 보존된 작은 단백질로 염색사 리모델링과 mRNA 생성과정에 관여한다. Sus1 단백질은 전사 보조활성자인 SAGA 복합체와 핵공과 연관된 TREX2 복합체 등, 핵에 존재하는 2개 복합체의 구성 요소이다. 분열효모 Schizosaccharomyces pombe의 유전체 데이터에서 Sus1의 이종상동체를 찾아 기능을 분석하였다. 4분체 분석 결과 이 유전자는 생장에 필수적이 아니었으나, Sus1 유전자를 결실시키면 낮은 온도에서 생장이 느렸으며, $poly(A)^+$ RNA도 핵 안에 약간 축적되는 표현형을 보였다. 또한 Sus1-GFP 단백질은 주로 핵에 존재하였다. Yeast two-hybrid 분석과 공동면역침전 실험에서 Sus1 단백질은 TREX-2 복합체의 또 다른 구성인자인 Sac3와 상호작용을 하였다. 이와 같은 결과들은 S. pombe의 Sus1 단백질도 역시 TREX-2 복합체의 구성인자로 mRNA 방출에 관여하고 있음을 시사한다.