• Journal of Korean Medicine Rehabilitation
• /
• v.30 no.1
• /
• pp.63-78
• /
• 2020

Objectives To review the epigenetic modifications involved in chronic pain and to improve individualized intervention for the chronic pain. Methods Focused literature review. Results Significant laboratory and clinical data support that epigenetic modifications have a potential role for development of chronic pain. Conclusions Epigenetic approach may identify mechanisms critical to the development of chronic pain after injury, and may provide new pathways and target mechanisms for future treatment and individualized medicine.

• Journal of Life Science
• /
• v.17 no.11
• /
• pp.1587-1592
• /
• 2007

Locus control region (LCR) is a cia-acting element which regulates the transcription of genes in developmental stage and/or tissue-specific pattern. Typically, LCR consists of several DNase I hypersensitive sites (HSs), where the binding motifs for transcriptional activators are present. The binding of activators to the HSs recruits chromatin modifying complexes to the LCR, opening chromatin structure and modifying histones covalently through the locus. LCR forms close physical contact with target gene located at a distance by looping away intervening region. In addition, non-coding RNA is transcribed from LCR toward target genes in continuously acetylated active domain. These structural and functional features of LCR suggest that the LCR plays many roles in chromatin activation and transcriptional regulation.

• Bulletin of the Korean Chemical Society
• /
• v.22 no.5
• /
• pp.507-513
• /
• 2001

Histones, nuclear proteins that interact with DNA to form nucleosomes, are essential for both the regulation of transcription and the packaging of DNA within chromosomes. The N-terminal domain of histone H4 which contains four acetylation sites at lysines, may play a separate role in chromatin structure from the remainder of the H4 chain. NMR data suggest that H4NTP peptide does have relating disordered structure at physiological pH, however, it has a defined structure at lower pH conditions. The solution structure calculated from NMR data shows a well structured region comprising residues of Val21-Asp24. In addition, our results suggest that the H4NTP prefers an extended backbone conformation at acetylation sites, however, it (especially Lys 12 ) became more defined structures after acetylation for its optimum function.

• Journal of Yeungnam Medical Science
• /
• v.38 no.3
• /
• pp.183-193
• /
• 2021

Since its discovery in 1780, lactate has long been misunderstood as a waste by-product of anaerobic glycolysis with multiple deleterious effects. Owing to the lactate shuttle concept introduced in the early 1980s, a paradigm shift began to occur. Increasing evidence indicates that lactate is a coordinator of whole-body metabolism. Lactate is not only a readily accessible fuel that is shuttled throughout the body but also a metabolic buffer that bridges glycolysis and oxidative phosphorylation between cells and intracellular compartments. Lactate also acts as a multifunctional signaling molecule through receptors expressed in various cells and tissues, resulting in diverse biological consequences including decreased lipolysis, immune regulation, anti-inflammation, wound healing, and enhanced exercise performance in association with the gut microbiome. Furthermore, lactate contributes to epigenetic gene regulation by lactylating lysine residues of histones, accounting for its key role in immune modulation and maintenance of homeostasis.

• Proceedings of the Korean Society of Applied Pharmacology
• /
• 2001.11a
• /
• pp.110-110
• /
• 2001

Histone deacetylase(HDAC), a neuclear enzyme that regulates gene trascription and the assembly of newly synthesized chromatin, has received much attention in recent literature. The explosion of activity in this field has yielded the cloning of a mammalian gene which encodes a complementary histone acetyl trasferases. Several cyclic tetrapeptide inhibitors of HDAC has been reported to affect the hyperacetylation of mammalian and plant histones. Apicidin, a natural product HDAC inhibitor recently isolated at Merck Research Laboratories, induces therapeutic applications as a broad spectrum antiprotozoal agent to multi-drug resistant malaria and a potential antitumor agnet. The biological activity of apicidin appears to be attributable to inhibition of apicocomplexan HDAC at low nanomolar concentrations.

• Applied Biological Chemistry
• /
• v.22 no.3
• /
• pp.173-180
• /
• 1979

SDS gel electrophoresis has been employed to examine the changes in distribution of three major classes of nuclear proteins extracted from isolated liver nuclei in response to refeeding of starved rats with a fat-free high carbohydrate diet and following insulin injection into streptozotocin-diabetic rats. The relative quantity of electrophoretically separated proteins in the fraction showed marked changes with 0.14 NaCl extracts, but not with histones and phenol soluble non-histone proteins. During 48h starvation at least five proteins ranging in molecular weight from 50,000 to 180,000 daltons decreased relative to normal controls while a protein with 36,000 daltons was increased. Refeeding the starved rats with a high carbohydrate diet reversed these changes over 24 h. Insulin injection into streptozotocin-diabetic rats increased levels of the set of five 0.14 M NaCl soluble proteins identified from refeeding experiment of starved rats. The 36,000 daltons protein was also diminished. These results indicate that changes in distribution of certain nuclear proteins in 0.14M NaCl extracts are associated with the control of nuclear activity ralated to known insulin-signalled modulation and induction of cytosolic lipogenic enzymes.

• Journal of Microbiology and Biotechnology
• /
• v.25 no.9
• /
• pp.1578-1582
• /
• 2015

Granzyme A (GzmA) was identified as a cytotoxic T lymphocyte protease protein expressed in the nucleus. A number of nuclear proteins are well known as GzmA substrates, and GzmA is related with caspase-independent apoptosis. Histones H1, H2B, and H3 were identified as GzmA substrates through in vitro experiment with purified nucleosome. Here, we demonstrated that histone H3 was cleaved by GzmA in vivo during staurosporine-induced cell death. Moreover, histone H3 cleavage was blocked by the GzmA inhibitor nafamostat mesylate and by GzmA knockdown using siRNA. Taken together, we verified that histone H3 is a real substrate for GzmA in vivo in the Raji cells treated by staurosporin.

• BMB Reports
• /
• v.31 no.5
• /
• pp.484-491
• /
• 1998

Acetylation of lysine residues within the aminoterminal domains of the core histones plays a critical role in chromatin assemhly as well as in regulation of gene expression. To study the biochemical function of histone acetylation, we have cloned a cDNA encoding the catalytic subunit of human histone acetyltransferase, Hat1. Analysis of the predicted amino acid sequence of human Hat1 revealed an open reading frame of 419 amino acids with a calculated molecular mass of 49.5 kDa and an isoelectric point of 5.5. The amino acid sequence of human Hat1 is homologous to those of known and putative Hat1 proteins from various species throughout the entire open reading frame. The recombinant human Hat1 protein expressed in bacteria possesses histone H4 acetyltransferase activity in vitro. Both RbAp46 and RbAp48, which participate in various processes of histone metabolism, enhance the histone acetyltransferase activity of the recombinant human Hat1, indicating that they are both able to functionally interact with the human Hat1 in vitro.

• ALGAE
• /
• v.18 no.3
• /
• pp.191-197
• /
• 2003

Histones are important proteins that interact with the DNA double helix to form nucleosome. Two putative histone genes, GjH2A-1 and GjH2A-2 were isolated from a red alga Griffithsia japonica. The putative open reading frame of GjH2A-1 and GjH2A-2 shared high similarity with the previously reported amino acid sequences of histone H2As. They have a motif consisting of seven amino acids A-G-L-Q-F-P-V, which matches the histone H2A motif [AC]-G-L-x-F-P-V. Phylogenetic trees were constructed from amino acid sequences of 38 histone H2As. The histone H2As were divided into two groups: major H2As and H2A.F/Z variants. The major histone H2A group consisted of animals, fungi, plants + green algae, and red algae H2A subgroups. The animal histone H2A subgroup was divided into vertebrates, echinoderms, nematodes, insects, and segmented worms H2As. The putative red algal histone genes, GjH2A-1 and GjH2A-2, constituted an independent lineage. This is the first report on red algal histone genes.

• Preventive Nutrition and Food Science
• /
• v.22 no.2
• /
• pp.81-89
• /
• 2017

Healthy aging has become a major goal of public health. Many studies have provided evidence and theories to explain molecular mechanisms of the aging process. Recent studies suggest that epigenetic mechanisms are responsible for life span and the progression of aging. Epigenetics is a fascinating field of molecular biology, which studies heritable modifications of DNA and histones that regulate gene expression without altering the DNA sequence. DNA methylation is a major epigenetic mark that shows progressive changes during aging. Recent studies have investigated aging-related DNA methylation as a biomarker that predicts cellular age. Interestingly, growing evidence proposes that nutrients play a crucial role in the regulation of epigenetic modifiers. Because various nutrients and their metabolites function as substrates or cofactors for epigenetic modifiers, nutrition can modulate or reverse epigenetic marks in the genome as well as expression patterns. Here, we will review the results on aging-associated epigenetic modifications and the possible mechanisms by which nutrition, including nutrient availability and bioactive compounds, regulate epigenetic changes and affect aging physiology.