• BMB Reports
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• 제51권5호
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• pp.211-218
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• 2018

Chromatin is an intelligent building block that can express either external or internal needs through structural changes. To date, three methods to change chromatin structure and regulate gene expression have been well-documented: histone modification, histone exchange, and ATP-dependent chromatin remodeling. Recently, a growing body of literature has suggested that histone tail cleavage is related to various cellular processes including stem cell differentiation, osteoclast differentiation, granulocyte differentiation, mammary gland differentiation, viral infection, aging, and yeast sporulation. Although the underlying mechanisms suggesting how histone cleavage affects gene expression in view of chromatin structure are only beginning to be understood, it is clear that this process is a novel transcriptional epigenetic mechanism involving chromatin dynamics. In this review, we describe the functional properties of the known histone tail cleavage with its proteolytic enzymes, discuss how histone cleavage impacts gene expression, and present future directions for this area of study.

• BMB Reports
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• 제32권4호
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• pp.345-349
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• 1999

We fused the promoter region of an H3.2 chicken histone gene, whose expression is dependent on the cell cycle, to the 5' coding region of an H3.3 chicken histone gene, which is expressed constitutively at a low level throughout the cell cycle. This fusion gene showed a cell cycle-regulated pattern of expression, but in a different manner. The mRNA level of the fusion gene increase during the S phase of the cell cycle by about 3.7-fold at 6 h and 2.7-fold at 12 h after the serum stimulation. The mRNA level of the intact H3.2 gene, however, increased by an average of 3.6-fold at 6 h and 8.7-fold at 12 h. This different expression pattern might be due to the differences in their 3' end region that is responsible for mRNA stability. The 3' end of the H3.2 mRNA contains a stem-loop structure, instead of a poly(A) tail present in the H3.3 mRNA. We also constructed a similar fusion gene using a H3.3 histone gene whose introns had been eliminated to rule out the possibility of involvement of the introns in cell cycle-regulated expression. The expression of this fusion gene was almost identical to the fusion gene made previously. These results indicate that the promoter region of the H3.2 gene is only partially responsible for its expression during the S phase of the cell cycle.

• Journal of Microbiology and Biotechnology
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• 제3권3호
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• pp.156-160
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• 1993

A chicken H2B histone gene was cloned and expressed in Rat 3 cell line. Its messenger RNA level was about 10 times higher during S phase than during $G_1$ phase. A chimeric chicken-yeast-chicken H2B histone gene was made to change some of wobble sequences of chicken H2B gene. When the chimeric H2B gene was transfected into the Rat 3 cell line, it showed a pattern of expression similar to that of the original chicken H2B gene. At least in this gene, it was concluded that the wobble sequences were not required for the cell-cycle regulated pattern of expression.

• BMB Reports
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• 제50권11호
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• pp.537-538
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• 2017

Hypoxia affects various physiological and pathophyological processes. Hypoxia changes the expression of hypoxia-responsive genes through two main pathways. First, hypoxia activates transcription factors (TF) such as Hypoxia-inducible Factor (HIF). Second, hypoxia decreases the activity of Jumonji C domain-containing histone demethylases (JMJDs) that require $O_2$ and ${\alpha}$-Ketoglutarate (${\alpha}$-KG) as substrates. The JMJDs affect gene expression through their regulation of active or repressive histone methylations. Profiling of H3K4me3, H3K9me3, and H3K27me3 under both normoxia and hypoxia identified 75 TFs whose binding motifs were significantly enriched in the methylated regions of the genes. TFs showing similar binding strengths to their target genes might be under the 'metabolic control' which changes histone methylation and gene expression by instant changing catalytic activities of resident histone demethylases.

• Molecules and Cells
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• 제43권10호
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• pp.841-847
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• 2020

Histone acetylation and deacetylation play central roles in the regulation of chromatin structure and transcription by RNA polymerase II (RNA Pol II). Although Hda1 histone deacetylase complex (Hda1C) is known to selectively deacetylate histone H3 and H2B to repress transcription, previous studies have suggested its potential roles in histone H4 deacetylation. Recently, we have shown that Hda1C has two distinct functions in histone deacetylation and transcription. Histone H4-specific deacetylation at highly transcribed genes negatively regulates RNA Pol II elongation and H3 deacetylation at inactive genes fine-tunes the kinetics of gene induction upon environmental changes. Here, we review the recent understandings of transcriptional regulation via histone deacetylation by Hda1C. In addition, we discuss the potential mechanisms for histone substrate switching by Hda1C, depending on transcriptional frequency and activity.

• 미생물학회지
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• 제40권3호
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• pp.226-229
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• 2004

염색질을 구성하는 histone 단백질 lysine 잔기에 histone acetylase에 의하여 결합된 acetyl기를 제거하는 histone deacetylase (HDAC)는 진핵세포 생물의 염색질 안정 파 및 유전자 발현에 매우 큰 영향을 미친다. 국내에서 분리된 영지의 HDAC 유전자를 클로닝 하고자 cDNA 및 genomic DNA를 대상으로 PCR을 수행한 결과 470bp의 cDNA유전자와, 585 bp, 589 bp 및 630 bp길이의 genomic DNA유전자 조각을 클로닝 하였다. 이들의 염기서열을 근거로 아미노산 서열을 다른 균류의 HDAC와 비교한 결과 59-72％의 상동성을 보였다.

• 한국어병학회지
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• 제35권1호
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• pp.121-128
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• 2022

Recent studies revealed that histone proteins are involved in innate immune responses during pathogen invasion as well as DNA packing. This study characterized the histone genes (H2A.V) of sevenband groupers and analyzed gene expression in NNV-infected sevenband groupers. The open reading frame (ORF) of H2A.V is 387 bp which encoded 128 amino acid residues. The deduced amino acid sequence of H2A.V harbor a highly conserved domain for H2A/H2B/H3 and H2A_C binding domain. Quantitative real-time PCR analysis showed that H2A.V had a high gene expression level in the brain and blood after being NNV-infected. An increase in extracellular histone protein in the blood has been identified as a biomarker for vascular function in humans. More research is required to understand histone's immune response at the protein level or in aquatic animals.

• BMB Reports
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• 제30권3호
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• pp.200-204
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• 1997

We eliminated introns from replication independent chicken H3.3 histone gene using a H3.3 cDNA clone and a genomic H3.3 clone. After introduction into Rat 3 cells, we observed its pattern of expression by analyzing mRNA from different phases of the cell cycle. Even without introns, the H3.3 gene was expressed constitutively at a low level throughout the cell cycle. This indicates that the introns in the H3.3 gene are not responsible for the cell cycle-independent expression of the gene. This result contradicts previous reports that suggested their importance in cell cycle regulated expression. We believe that other regions of the gene, promoter, coding region, and/or 3'-end of the gene, are involved in its expression pattern.

• BMB Reports
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• 제53권5호
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• pp.266-271
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• 2020

Breast cancer encompasses a major portion of human cancers and must be carefully monitored for appropriate diagnoses and treatments. Among the many types of breast cancers, triple negative breast cancer (TNBC) has the worst prognosis and the least cases reported. To gain a better understanding and a more decisive precursor for TNBC, two major histone modifications, an activating modification H3K4me3 and a repressive modification H3K27me3, were analyzed using data from normal breast cell lines against TNBC cell lines. The combination of these two histone markers on the gene promoter regions showed a great correlation with gene expression. A list of signature genes was defined as active (highly enriched H3K4me3), including NOVA1, NAT8L, and MMP16, and repressive genes (highly enriched H3K27me3), IRX2 and ADRB2, according to the distribution of these histone modifications on the promoter regions. To further enhance the investigation, potential candidates were also compared with other types of breast cancer to identify signs specific to TNBC. RNA-seq data was implemented to confirm and verify gene regulation governed by the histone modifications. Combinations of the biomarkers based on H3K4me3 and H3K27me3 showed the diagnostic value AUC 93.28% with P-value of 1.16e-226. The results of this study suggest that histone modification analysis of opposing histone modifications may be valuable toward developing biomarkers and targets for TNBC.

• BMB Reports
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• 제36권1호
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• pp.110-119
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• 2003

The acetylation state of histone is reversibly regulated by histone acetyltransferase (HAT) and deacetylase (HDAC). An imbalance of this reaction leads to an aberrant behavior of the cells in morphology, cell cycle, differentiation, and carcinogenesis. Recently, these key enzymes in the gene expression were cloned. They revealed a broad use of this modification, not only in histone, but also other proteins that involved transcription, nuclear transport, and cytoskeleton. These results suggest that HAT/HDAC takes charge of multiple-functions in the cell, not just the gene expression. HDAC is especially known to play an important role in carcinogenesis. The enzyme has been considered a target molecule for cancer therapy. The inhibition of HDAC activity by a specific inhibitor induces growth arrest, differentiation, and apoptosis of transformed or several cancer cells. Some of these inhibitors are in a clinical trial at phase I or phase II. The discovery and development of specific HDAC inhibitors are helpful for cancer therapy, and decipher the molecular mode of action for HDAC.