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Role of Histone Methyltransferase in Breast Cancer
Published in Meenu Gupta, Rachna Jain, Arun Solanki, Fadi Al-Turjman, Cancer Prediction for Industrial IoT 4.0: A Machine Learning Perspective, 2021
Surekha Manhas, Zaved Ahmed Khan
Gene expression regulation by means of histone-modifying enzymes marks a dominant mechanism that regulates the differentiation and development of cells. Posttranslationally, modifications of histones could be carried out by methylation, acetylation, phosphorylation, ubiquitination, and sumoylation [75]. In particular, methylation at lysine residues of histone protein is the chief regulator of active gene expression. MLL1-dependent H3K4me3 and EZH2-dependent H3K27me3 EZH2, H3K27me3, are the foremost well-known modifications that are strongly related to recognizable gene expression also with repression [76–80]. Various other specific histone-methylation regions have been recognized to be more critical, including H3K9 histone residue with G9a-dependent H3K9me2 and Suv39h (1–2)-mediated H3K9me3. All these display crucial functional roles in cellular differentiation and functions, too [81–84]. Available data suggest that H3K9me2 has also been found to modify euchromatin. In addition, it also is dynamically able to regulate the gene expression of many differentiating cells.
The Precision Medicine Approach in Oncology
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Histone modifications occur in tumor cells in different types of histone proteins, their variants and on individual residues within them. These involve modifications to chemical functional groups, including variations to the degree of methylation. In general, acetylation of histones signifies transcription activation, while the effect of methylation of histones is less specific and dependent on the amino acid type and position of the histone tail. The generally accepted mechanism for enhanced gene transcription through acetylation of lysine residues is that nonacetylated lysine residues possess side-chains terminating in positively charged (i.e., protonated) amino groups which keep the chromatin condensed through electrostatic charges. Once acetylated, the positive charge is lost, and the chromatin opens (i.e., de-condenses), thus exposing the DNA to transcription-promoting proteins including transcription factors. Also, the pattern of expression of histone-modifying enzymes is distinct in tumor versus healthy cells. These modifications to histone proteins can be reliably and specifically detected by mass spectrometry techniques. For example, overexpression of the histone demethylase PLU-1 has been detected in breast cancer cells, and variations of expression of the histone deacetylase HDAC1 has been detected in hematological, colon, and endometrial cancer cells.
The Role of Epigenetics in Skeletal Muscle Adaptations to Exercise and Exercise Training
Published in Peter M. Tiidus, Rebecca E. K. MacPherson, Paul J. LeBlanc, Andrea R. Josse, The Routledge Handbook on Biochemistry of Exercise, 2020
The heritability of histone modifications and variants has been debated in the literature. Most histone modifications are thought to be highly dynamic, in line with the pulsatile nature of transcriptional responses. Indeed, the half-life of histone acetylation was thought to be 1–2 minutes (26); however, more recent studies suggest that some site-specific acetylation marks have a half-life of up to 30 hours (70). Nonetheless, other histone modifications are more stable, such as methylation, with a half-life of up to a number of days (68). This is sufficient to allow histone-modifying enzymes to replicate modifications from inherited histones to new histones throughout mitotic cell division. Indeed, some histone methyltransferases can recognize and amplify pre-existing histone methylation patterns (32). The influence of epigenetic inheritance on skeletal muscle phenotype will be discussed later in this chapter; however, it is likely that both histone modifications and variants play a role in retaining epigenetic information that influences transcriptional responses.
Epigenetic control of skin immunity
Published in Immunological Medicine, 2023
The mechanisms of epigenetic regulation are classified into three major categories: DNA methylation, post-translational histone modification, and chromatin remodeling [6,9,10]. This review focuses on the latter two categories. Post-translational histone modification facilitates the addition or removal of acetyl or methyl groups on histones via covalent binding by histone modifying enzymes [11]. Acetylation decreases the positive charge of histones and consequently reduces the affinity between histones and DNA. This results in the loosening of chromatin structure which is associated with enhanced transcriptional activity. The chromatin status and associated transcriptional activity regarding methylation depend on the residues to be modified and the type of methylation [7]. Combinations of different histone modifications are associated with the relaxation or condensation of chromatin structures, affecting transcriptional activity. The histone modifying enzymes that typically mediate the addition or removal of chemical groups on histones via covalent binding are referred to as epigenetic players. These include the ‘writers’ that introduce chemical modification on histones, ‘readers’ that recognize these modifications, and ‘erasers’ that remove the modification from histones [12]. The representative histone modification enzymes are summarized in Table 1.
Inhibition of histone demethylase JMJD1C attenuates cardiac hypertrophy and fibrosis induced by angiotensin II
Published in Journal of Receptors and Signal Transduction, 2020
Shenqian Zhang, Ying Lu, Chenyang Jiang
It is well known that histone modifications play key roles in gene transcription. Over the past decades, a great deal has demonstrated that histone methylation plays a key role in cardiac remodeling [7–9]. In our study, we identified a H3K9me2 and H3K9me1 demethylase JMJD1C involved in cardiac hypertrophy and fibrosis induced by pathological stress. JMJD1C is a global regulator of chromatin remodeling and gene expression. Gene expression is mediated by transcription factors and histone-modifying enzymes. Many different histone-modifying enzymes, including HDACs, HATs, HMTs, and HDMs, contribute to the dynamic regulation of chromatin structure and function, with concomitant impacts on gene transcription [28–30]. Unlike transcription factors that often have on-off effects on gene transcription, the effects of histone-modifying enzymes on gene transcription are often modulatory. This modulatory effect can be context- and gene-dependent such that only those genes exceeded the threshold will yield a phenotype and be identified. In our study, we did not identify what genes were different in JMJD1C knockdown and control cells, and which was regulated by histone methylation change. It will be interesting to identify these genes using RNA-seq and ChIP-seq combined analysis to further investigate the relationship between JMJD1C-regulated H3K9me2 marks which ultimately determines the transcriptional state of the gene as either active, repressed, or poised for activation.
Recent advances in histone modification and histone modifying enzyme assays
Published in Expert Review of Molecular Diagnostics, 2019
Fei Ma, Su Jiang, Chun-yang Zhang
Histone modifying enzymes catalyze the formation of a variety of histone modifications and play important roles in many normal cellular functions.Histone modifying enzymes and histone modifications may serve as the disease biomarkers because their abnormal activities and levels are closely associated with a variety of human disease.Many new methods have been developed in recent years for the detection of histone modifying enzymes and histone modifications based on fluorescent, bioluminescent, colorimetric, electrochemical, SERS, and mass spectrometry strategiesThese methods exhibit good performance in both in vitro and in vivo assaysThe introduction of aptamers and novel nanomaterial-based probes may facilitate the in vivo detection of different kinds of histone modifications and histone modifying enzymes.