The EPIMODIFIER™ screening system provides a platform for conveniently screening modulators that target site-specific histone modifications. Site-specific histone modifications directly and indirectly impact transcriptional regulation and the direction of various cellular processes. The biological influences achieved by various histone modifying enzymes eventually require that histone be modified. Epigenetic modifications can be modulated by directly inhibiting modifying enzymes or blocking co-factor recruiting pathways. Development of these modulators would lead to the development of new therapeutic agents and improvement in disease treatment, especially cancer therapy.
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Available Target Modifications
Histone Acetylation Profiling
- Acetylation of histones, has been involved in the regulation of chromatin structure and the recruitment of transcription factors to gene promoters. Histone acetyltransferases (HATs) and histone deacetylases (HDACs) play a critical role in controlling histone H3 acetylation. Histone acetylation is tightly involved in cell cycle regulation, cell proliferation, and apoptosis. An imbalance in the equilibrium of histone acetylation has been associated with tumorigenesis and cancer progression. Histone acetylation may be increased by inhibition of HDACs and decreased by HAT inhibition. The reversible lysine acetylation of histone may play a vital role in the regulation of many cellular processes including chromatin dynamics and transcription, gene silencing, cell cycle progression, apoptosis, differentiation, DNA replication, DNA repair, nuclear import, and neuronal repression. Detecting if histone is acetylated at its lysine residue would provide useful information for further characterizing the acetylation patterns or sites, thereby leading to a better understanding of epigenetic regulation of gene activation, and development of HAT or HDAC-targeted drugs.
- Target Modifications: total histone H3, total histone H4, H3K9, H3K14, H3K18, H3K23, H3K56, H4K5, H4K8, H4K12, H4K16
Histone Methylation Profiling
- Histone methyltransferases catalyze methylation of histone at lysine or arginine in mammalian cells. Lysine or arginine residues can be mono-di or tri-methylated, each of which can differentially regulate chromatin structure and transcription. Along with other histone modifications such as phosphorylation, this enormous variation leads to a multiplicity of possible combination of different modifications Histone methylation may serve as a global epigenetic mark. Alterations of global histone methylation is also found to be involved in some pathological processes such as cancer progression. The global histone methylation can be changed by inhibition or activation of HMTs.
- Target Modifications: H3K4, H3K9, H3K27, H3K36, H3K79, H3R2, H3R17, H4R3
Histone Phosphorylation Profiling
- The phosphorylation of histone H3 at serine or threonine conserved through eukaryotes, and an increase in phosphorylation has been shown to correlate with gene activation and cell growth.. It was observed that H3 phosphorylation (ser10) is critical for neoplastic cell transformation. Several protein kinases, including aurora B, PPI, and PKC, are responsible for histone phosphorylation. Inhibition or activation of these protein kinases can cause the change in intracellular histone phosphorylation. Inhibition or or activation of histone phosphorylation, would provide useful information for better understanding the pathological process of some diseases, and for protein kinase-targeted drug development.
- Target Modifications: H2AX, H2B, H3 (ser10), H3 (ser28), H3 (Thr11)
Histone SUMOylation Profiling
- SUMOylation is a post-translational modification involved in various cellular processes, such as nuclear-cytosolic transport, transcriptional regulation, apoptosis, protein stability, response to stress, and progression through the cell cycle. SUMO proteins are similar to ubiquitin. There are 3 confirmed SUMO isoforms in humans: SUMO-1, SUMO-2, and SUMO-3. Sumoylation is directed by an enzymatic cascade analogous to that involved in ubiquitination. SUMOylation of target proteins in vivo has been shown to cause a number of different outcomes, including altered localization and binding partners. In many cases, sumoylation of transcriptional regulators correlates with inhibition of transcription. Thus, detection of in vivo protein sumoylation (SUMO conjugation) would provide useful information for understanding SUMO modification that emerges as an important control mechanism regulating the activity of many nuclear proteins, as well for protein sumoylation-targeted drug development.
- Target Modifications: histone H3, histone H4, HDAC1, HDAC2, DNMT1, DNMT3A, EZH2
Proper sample preparation along with the appropriate quality control methods on your end will allow the greatest chance for assay success. Please follow all guidelines for sample requirements, packaging and labeling, and shipping which are outlined on the Submission Instructions page and Drug Discovery Sample Preparation Instructions.
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Want more information on our Histone Modification Profiling and Drug Discovery services or interested in customizing your research project? We’re here to help! Get in touch with one of our highly knowledgeable epigenetic services experts by calling toll-free at 1-877-374-4368 or emailing services @ epigentek.com.