Histones, nucleosomes and epigenetic substrates

Fully customizable, freshly prepared, to suit your needs – contact us to find out more

How we support your epigenetic drug discovery or research process

Epigenetic screening reagents

Catalog Nucleosomes – freshly prepared to every order

We have validated and qualified DNA templates and histone octamers on stock. Upon your order, we assemble the required amount of nucleosome and perform extensive QC to ensure reproducible quality. This allows us to re-supply nucleosomes at much larger quantities but at the same saturation degree and quality.

Educts as control reagents or for custom applications

We are proud of the Histones, Octamers and DNA Templates that we prepare using our proprietary production processes. We share those reagents with you for your custom applications in epigenetic research and drug discovery

  • Pure Histone proteins as lyophilized powders
  • Histone Octamers provided as assembly-ready solutions
  • DNA templates for mono- and oligonucleosome assembly
  • A starter set of lab consumables – pipet tips and vials with low-binding surfaces, validated by us – low nucleosome binding

Custom nucleosome production

Your requirements

We engage with you to understand the requirements for your epigenetic screening question

Our design

We propose a set of custom nucleosomes to address:

  • The requirements of the epigenetic target
  • PTM’s, histone variants, cancer mutations
  • DNA length
  • Detection reagents (Fluorophores, biotin, linkers, attachment sites)

Test sample production

We produce several test samples to address

  • Impact of PTMs on binding / Km
  • Test of several attachment sites for detection reagents to avoid interference
  • DNA length/nucleosome spacing to mimic cellular chromatin
  • Saturation degree

Test in your hands

You are the experts in assay optimization and test

    • Reaction parameters (Km, Kd, Vi, S/B, S/N, Z’) of the individual nucleosome preparations
    • Reagent stability under your experimental conditions
    • Scalability of reaction (384 – 1536 scale)
    • We work closely with you and can provide advice on handling procedures and optimization parameters that are specific to nucleosomes

Upscales

We upscale production of the most promising nucleosome variants for final assay optimization and HTS. Our proprietary process allows producing hundreds of milligrams to support full pharma scale HTS campaigns

Hit confirmation & triaging

Our support does not stop at the HTS stage. We provide further nucleosomes as control reagents, for mode-of-action studies, for biophysical profiling and structural biology

Contact us for quotes and further information

Email: octamer@volition.com

FAQ's

Epigenetic mechanisms promise to open new avenues to drug discovery because they allow interfering with the most basic processes of transcriptional regulation. However, with now > 15 years of pharma experience in drugging epigenetic mechanisms, we understand some of the culprits in epigenetic drug discovery:

  • Epigenetic targets generally are multi-domain or multiprotein complexes
  • Some epigenetic targets are activated by marks they don’t place (e.g. Dot1L methyltransferase is activated by ubiquitin-H2B, UHRF1 E3 ligase is activated by hemimethylated nucleosomal DNA)
  • Affinities for non-natural substrates are generally low (e.g. µM for peptides, nM for nucleosomes)

This is why nucleosomes offer the unique opportunity to provide disease-relevant substrates to epigenetic targets – both for academic research and drug discovery

If not requested otherwise, we always provide our nucleosomal stock solutions in a Triethanolamine buffer with low ionic strength. Our nucleosomes are never stored in the presence of glycerol or sugars that are commonly used as cryo-protecting agents as these might interfere with assay development. While being stored at 4°C, our nucleosomes are exceptionally stable and we have re-used nucleosome stocks that were stored for years. However, they are prone to microbial contamination. Therefore, we supplement our stocks with 0.03% NaN3 for long-term storage.

This is our favorite storage buffer:

10mM TEA, pH = 7.5

20mM NaCl

0.1mM EDTA

0.03% NaN3