HDAC Spectrum^SM HAT Spectrum^SM

RBC offers a full spectrum of assays for HDACs, Sirts and HATs:

Lysine acetylation in chromatin, specifically the N-terminal tails of histones, is, to a first approximation, associated with gene activation and its absence with gene silencing. Perhaps the most studied of the “epigenetic” regulatory post-translational modifications, lysine acetylation also occurs on an extensive list of non-histone proteins (~1750 in humans), including a variety of transcription factors (e.g. p53), tubulin and tau, the microtubule-associated protein involved in neurofibrillary tangle formation in Alzheimer’s disease. The acetylation/deacetylation regulatory system depends on two metabolic cofactors, acetyl-CoA (acetyltransferasecosubstrate) and NAD+ (class III histone deacetylase (sirtuin) cosubstrate), and there is growing evidence of its regulatory role in metabolism.

Unsurprisingly, given acetylation’s profound regulatory functions, a variety of diseases are associated with dysfunction of the enzymes that add acetyl groups, histone acetyltransferases (HATs), and those that remove them, the HDACs (Histone Deacetylases, class I/II) and sirtuins (SIRTs, NAD+-dependent/class III HDACs). HDAC inhibitors have anti-proliferative effects on cancer cells and there are now two pan-HDAC inhibitors (HDACi’s), Vorinostat (SAHA) and Istodax (romidepsin) approved as drugs for cutaneous T-cell lymphoma (CTCL). Isoform-specific HDACi’s, targeting, for example, HDAC6, may represent the next wave in successful anti-cancer HDAC drug discovery. Aside from the well-known cancer example, possible indications for class I/II HDAC inhibitors include diabetes, high cholesterol, cardiac hypertrophy/inflammation, inflammatory bowel diseases and neurodegenerative disorders. Sirtuin activators are being pursued as a therapeutic strategy for diabetes, neurodegenerative disorders and aging-associated diseases in general. Inhibition of HATs is a potential route to therapies for neurodegeneration and chronic obstructive pulmonary disease (COPD).

RBC’s HAT assays are radioisotope-based filtration assays. This “Gold Standard” approach can be used regardless of whether the substrate is a peptide, histone, nucleosome or non-histone protein. With ~1750 lysine-acetylated proteins in the human proteome, RBC’s HAT SpectrumSM assays provide an important advantage in terms of assay flexibility as well as “Gold Standard” quality.

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