EpiCypher was founded in 2012 by Drs. Mark Bedford, Or Gozani, Brian Strahl, and James Bone in response to the growing demand for high-quality reagents and tools to study chromatin regulation and enable epigenetics-focused drug development.

EpiCypher is the global leader in recombinant nucleosome manufacturing and development. Using proprietary methods, we are continuously adding to the world’s largest collection of highly pure modified recombinant “designer” nucleosomes (dNucs). EpiCypher’s broad dNuc diversity is providing a powerful tool to decipher the histone code and accelerate drug development. Shah et al., Wang et al., and Weinburg et al. (see below) are just a few examples of the many benefits of using nucleosome substrates for epigenetics studies.

EpiCypher leverages dNuc technology for a wide range of applications, including: SNAP-ChIP® Spike-in Controls (for antibody profiling and quantitative ChIP), EpiDyne® substrates (for characterizing chromatin remodeling enzyme complexes and inhibitors), and dCypher™ assays (for interrogation of epigenetic protein-histone PTM binding interactions). We also offer a suite of high-quality recombinant histone binding proteins, enzymes, peptides, antibodies, and custom assay development services to complement these platforms.

EpiCypher continuously pushes technology boundaries to deliver innovative products, solutions, and services to epigenetics and chromatin biology researchers. Most recently, EpiCypher has been at the leading edge of chromatin mapping technology improvements with the recent launch of the highly sensitive epigenomic mapping CUTANA assays for ChIC, CUT&RUN, and CUT&Tag.

From our strong scientific expertise and rigor to our focus on customer success, EpiCypher is proud to be a company For Scientists, By Scientists.

EpiCypher Co-Authored Publications

Neutrophil Extracellular Trap Formation and Syndecan-1 Shedding are Increased after Trauma. Shock. Online ahead of print (2021). (PMID: 33534396)

Goswami G, MacArthur T, Bailey K, Spears G, Kozar RA, Auton M, Dong J-F, Key NS, Heller S, Loomis E, Hall NW, Johnstone AL & Park MS.

Neutrophil extracellular traps (NETs) are webs of citrullinated nuclear proteins released during inflammatory processes and can be detected in human plasma by probing for histone H3 citrullination (H3Cit) on circulating nucleosomes. NETs have been linked to numerous human pathologies and are associated with increased coagulation and thrombosis. In this paper, EpiCypher collaborated with Dr. Myung Park’s group to study markers of NETs in patients following traumatic injury, applying EpiCypher’s quantitative CitH3 ELISA assay. Our results demonstrate that high levels of H3Cit nucleosomes in plasma may be a useful biomarker for trauma-related thrombosis.

Separation and Characterization of Endogenous Nucleosomes by Native Capillary Zone Electrophoresis – Top-Down Mass Spectrometry (nCZE-TDMS). Anal. Chem. 93, 5151-5160 (2021). (PMID: 33749242)

Jooß K, Schachner LF, Watson R, Gillespie ZB, Howard SA, Cheek MA, Meiners MJ, Licht JD, Keogh M-C & Kelleher NL.

This paper describes the rigorous development of a three-tier tandem mass spectrometry approach that enables comprehensive and ultra-sensitive analysis of chromatin proteoforms. The first tier uses Nuc-MS (Schachner et al.) to determine the mass of intact mononucleosomes. Second, constituent histones from nucleosomes are analyzed, including detection of PTMs; and third, fragmented histone peptides are sequenced. The nCZE-TDMS method was developed by the Kelleher lab in collaboration with EpiCypher and used EpiCypher dNuc substrates for optimization against a pure, defined nucleosome population.

Complex-dependent histone acetyltransferase activity of KAT8 determines its role in transcriptional regulation and cellular homeostasis. Mol. Cell. Online ahead of print (2021). (PMID: 33657400)

Radzisheuskaya A, Shliaha PV, Grinev V, Shlyueva D, Koche R, Gorshkov V, Kovalchuk S, Zhan Y, Rodriguez KL, Johnstone AL, Keogh M-C, Hendrickson RC, Jensen ON & Helin K.

Histone lysine acetylation is an established hallmark of open chromatin. However, the regulation of acetyl marks at distinct sites across the genome is not fully understood. This study demonstrates context-specific activity of the acetyltransferase KAT8, which targets distinct H4 lysine residues dependent on its associated protein complexes. The EpiCypher K-AcylStat dNuc panel was used to develop a multiplex screening assay to identify H4K16ac antibodies that exhibit exquisite target specificity and were used to help elucidate KAT8 function by ChIP-seq.

Decoding the Protein Composition of Whole Nucleosomes with Nuc-MS. Nat. Methods 18, 303-308 (2021). (PMID: 33589837)

Schachner LF, Jooβ K, Morgan MA, Kafader JO, Piunti A, Iwanaszko M, Meiners MJ, Cheek MA, Burg JM, Howard SA, Keogh M-C, Shilatifard A & Kelleher NL.

Mass spectrometry represents a powerful approach for characterization of the histone code. However, existing methods for mass spec of chromatin utilize bulk fragmented histones, greatly complicating the analysis of co-occurring histone PTMs within nucleosome subunits and obscuring cooperative functions. In this paper, EpiCypher collaborated with the Kelleher lab to develop Nuc-MS, a novel approach that enables detection of histone PTMs and variants within intact mononucleosomes. Nuc-MS was established using defined dNuc substrates from EpiCypher, providing robust validation for this breakthrough technology.

Examining the roles of H3K4 methylation states with systematically characterized antibodies. Mol. Cell 72, 162-177 (2018). (PMID: 30244833)

Shah RN, Grzybowski AT, Cornett EM, Johnstone AL, Dickson BM, Boone BA, Cheek MA, Cowles MW, Maryanski D, Meiners MJ, Tiedemann RL, Vaughan RM, Arora N, Sun ZW, Rothbart SB, Keogh MC & Ruthenberg AJ.

This study established SNAP-ChIP Recombinant Nucleosome Spike-ins as a robust and essential technology for defining histone PTM antibody binding in ChIP experiments. Direct comparison of SNAP-ChIP (also known as ICeChIP) Spike-ins and histone peptide arrays revealed that modified histone peptides had no predictive ability for antibody performance in ChIP, and many “ChIP-grade” antibodies to H3K4me1, me2, and me3 exhibited off-target binding and poor pull-down efficiency. Instead, SNAP-ChIP Spike-in Controls were able to accurately characterize antibody performance within the context of a ChIP assay.

Chromatin Immunoprecipitation (ChIP) to Study DNA–Protein Interactions. Methods Mol. Biol. 2261, 323-343 (2021). (PMID: 33420999)

Small EC, Maryanski DN, Rodriguez KL, Harvey KJ, Keogh M-C & Johnstone AL

EpiCypher provides detailed methods for native ChIP-seq experiments and guidance on best practices to ensure robust, reliable data. Importantly, we describe how SNAP-ChIP® spike-in controls can be used in ChIP-seq experiments to monitor on-target specificity and enrichment efficiency, as well as for quantitative data normalization.

SETD5-coordinated chromatin reprogramming regulates adaptive resistance to targeted pancreatic cancer therapy. Cancer Cell 37, 834-849.e13 (2020). (PMID: 32442403)

Wang Z, Hausmann S, Lyu R, Li T, Lofgren SM, Flores NM, Fuentes ME, Caporicci M, Yang Z, Meiners MJ, Cheek MA, Howard SA, Zhang L, Elias JE, Kim MP, Maitra A, Wang H, Bassik MC, Keogh MC, Sage J, Gozani O &Mazur PK.

This study utilized EpiCypher’s library of dNucs to identify epigenetic pathways underlying the development of drug-resistant pancreatic cancer. Several of our lysine-acetylated recombinant nucleosomes were used to characterize the novel SETD5-HDAC3-G9a corepressor complex, revealing SETD5 as a master regulator that coordinates selective inactivation of key genes required for drug sensitivity.

H3K36me2 recruits DNMT3A and shapes the intergenic DNA methylation landscape. Nature 573, 281-286 (2019). (PMID: 31485078)

Weinberg DN, Papillon-Cavanaugh S, Chen H, Yue Y, Chen X, Rajagopalan KN, Horth C, McGuire JT, Xu X, Nikbakht H, Lemeisz AE, Marchione DM, Marunde MR, Meiners M, Cheek M, Keogh MC, Bareke E, Djedid A, Harutyunyan AS, Jabado N, Garcia BA, Li H, Allis CD, Majewski J & Lu C.

Here, dCypher nucleosome panels illuminated the binding preference of chromatin reader DNMT3A towards NSD1-catalyzed H3K36me2, highlighting the importance of the nucleosome context when defining histone PTM interactions. Notably, alterations in each of these chromatin regulators results in childhood overgrowth syndromes (mutation of DNMT3A is associated with Tatton-Brown-Rahman syndrome, while changes in NSD1 cause Sotos syndrome). This work established a new regulatory link between the two growth disorders, as loss of NSD1 leads to misregulated localization of DNMT3A and altered DNA methylation in intergenic regions.

Histone H1 loss drives lymphoma by disrupting 3D chromatin architecture. Nature 589, 299-305 (2021). (PMID: 33299181)

Yusufova N, Kloetgen A, Teater M, Osunsade A, Camarello JM, Chin CR, Doane A, Venters BJ, Portillo-Ledesma S, Conway J, Bott M, Philips J, Elemento O, Scott DW, Beguelin W, Licht JD, Kelleher N, Staudt LM, Skoultchi AI, Keogh M-C, Apostolou W, Mason C, Imielinski M, Schlick T, David Y, Tsirigos A, Allis CD, Soshnev AA, Cesarman E & Melnick AM.

Although linker H1 histone proteins are often mutated in B-cell lymphoma, the downstream impacts of these mutant alleles are not well known. In this study, Yusufova et al. demonstrate that H1 histones are bona fide tumor suppressor proteins, which are required to package early developmental genes into transcriptionally inaccessible heterochromatin. EpiCypher CUTANA CUT&RUN assays were key for analyzing changes in heterochromatin structure in rare germinal center B cells, as standard ChIP-seq assays lack the sensitivity to reliably profile from limited primary cell samples.