Histone deacetylases (HDACs) remove acetyl moieties from lysine residues of histones and other proteins to induce epigenetic change to DNA, and hence are important regulators of gene expression. Within the skin, they play a role in regulating keratinocyte proliferation and differentiation. To date, four classes of the HDACs have been identified: Class I (HDAC1, HDAC2, HDAC3, and HDAC8), class II HDACs (HDAC4, HDAC5, HDAC6, HDAC7, HDAC9, and HDAC10), class III (SIRT1-7) and class IV (HDAC11) but their role in keratinocyte biology is largely unknown. In this study, HDAC activity and abundance of class I, II, and IV HDACs were assessed in HaCaT cells and in primary human keratinocytes from juvenile (n = 5, mean age: 4yrs), middle-aged (n = 4, mean age: 50yrs) and elderly (n = 4, mean age: 81yrs) donors. We found that HDAC activity was significantly increased in middle-aged keratinocytes, as compared to juvenile keratinocytes (P<0.01); however, significantly lower HDAC activity was found in elderly keratinocytes compared to keratinocytes derived from middle-aged donors (P<0.01) and HaCaT cells (P<0.05). Next, the abundance of class I, II and IV HDACs was determined by Western blot analysis. We found no significant difference in class I, II and IV HDAC abundance as a function of donor age; however, HaCaT cells had significantly higher abundance of HDAC1, HDAC2, HDAC3 and HDAC5, as compared with primary human keratinocytes. Taken together, these data suggest that HDAC activity significantly changes throughout the life course. Further studies exploring these changes are warranted at both the transcriptional and translational level using primary keratinocytes to better understand the role of epigenetic tuning in keratinocyte differentiation and ageing.

ESDR230 - Investigating the role of histone deacetylases in human epidermis

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.