• BMB Reports
• /
• v.32 no.4
• /
• pp.345-349
• /
• 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
• /
• v.3 no.3
• /
• pp.156-160
• /
• 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
• /
• v.50 no.11
• /
• pp.537-538
• /
• 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
• /
• v.43 no.10
• /
• pp.841-847
• /
• 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.

• BMB Reports
• /
• v.30 no.3
• /
• pp.200-204
• /
• 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
• /
• v.53 no.5
• /
• pp.266-271
• /
• 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.

• Journal of fish pathology
• /
• v.35 no.1
• /
• pp.121-128
• /
• 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.

• Journal of Life Science
• /
• v.30 no.8
• /
• pp.713-721
• /
• 2020

Adipogenesis as a model system is needed to understand the molecular mechanisms of human adipocyte biology and the pathogenesis of obesity, diabetes, and other metabolic syndromes. Many relevant studies have been conducted with a focus on gene expression regulation and intracellular signaling relating to Peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein alpha (C/EBPα), which are master adipogenic transcription factors. However, epigenome regulation of adipogenesis by epigenomic modifiers or histone mutations is not fully understood. Histone methylation is one of the major epigenetic modifications on gene expression in mammals, and histone H3 lysine methylation (H3Kme) in particular implicates cell differentiation during various tissue and organ development. During adipogenesis, cell type-specific enhancers are marked by histone H3K4me1 with the active enhancer mark H3K27ac. Mixed-lineage leukemia 4 (MLL4) is a major H3K4 mono-methyltransferase on the adipogenic enhancers of PPARγ and C/EBPα loci. Thus, MLL4 is an important epigenomic modifier for adipogenesis. The repressive mark H3K27me3 is mediated by the enzymatic subunit Enhancer zeste homolog 2 (EZH2) of the polycomb repressive complex 2. EZH2-mediated H3K27 tri-methylation on the Wnt gene increases adipogenesis because WNT signaling is a negative regulator of adipogenesis. This review summarizes current knowledge about the epigenomic regulation of adipogenesis by histone H3 lysine methylation which fundamentally regulates gene expression.

• Journal of Life Science
• /
• v.21 no.4
• /
• pp.616-620
• /
• 2011

Lysine residues of histone H3 and H4 are covalently modified in the chromatin of eukaryotic cells. Lysine 27 in histone H3 was acetylated (H3K27ac) or methylated at three levels; mono-, di-, and trimethylation (H3K27me1, H3K27me2, and H3K27me3). These modifications at H3K27 were related with gene transcription and/or chromatin structure in distinct patterns. Generally, H3K27ac and H3K27me1 were enriched in active chromatin, such as the locus control region or transcriptionally active genes, while transcriptionally inactive genes were highly marked by H3K27me2 and H3K27me3. These modifications appear to have been catalyzed by distinct histone-modifying enzymes. Recent studies suggest that the four kinds of modifications at H3K27 have inter-correlation in gene transcription or chromatin structure formation.

• Genomics & Informatics
• /
• v.10 no.3
• /
• pp.145-152
• /
• 2012

Chromatin structure and dynamics that are influenced by epigenetic marks, such as histone modification and DNA methylation, play a crucial role in modulating gene transcription. To understand the relationship between histone modifications and regulatory elements in breast cancer cells, we compared our chromatin immunoprecipitation sequencing (ChIP-Seq) histone modification patterns for histone H3K4me1, H3K4me3, H3K9/16ac, and H3K27me3 in MCF-7 cells with publicly available formaldehyde-assisted isolation of regulatory elements (FAIRE)-chip signals in human chromosomes 8, 11, and 12, identified by a method called FAIRE. Active regulatory elements defined by FAIRE were highly associated with active histone modifications, like H3K4me3 and H3K9/16ac, especially near transcription start sites. The H3K9/16ac-enriched genes that overlapped with FAIRE signals (FAIRE-H3K9/14ac) were moderately correlated with gene expression levels. We also identified functional sequence motifs at H3K4me1-enriched FAIRE sites upstream of putative promoters, suggesting that regulatory elements could be associated with H3K4me1 to be regarded as distal regulatory elements. Our results might provide an insight into epigenetic regulatory mechanisms explaining the association of histone modifications with open chromatin structure in breast cancer cells.