Interest in epigenetics continues to grow, with the field often framed as relevant to health. Congruent with this, mediatisations of epigenetics exist that can be expected to help shape perspectives about its applications. Yet, while scholars have researched public framings of epigenetics within texts (eg, newspapers), there has been little attention to how it is communicated through audio-visual media—despite the clear significance of this genre internationally. Accordingly, this paper examines how creators of popular YouTube videos depict epigenetics. We report on a critical, thematic analysis of 10 highly viewed videos on epigenetics, attending to how these explain the field, present knowledge from it as ‘empowering’ and apportion personal responsibility. We explore how the purported novelty of epigenetics is narrated in the process, and how these configurations of epigenetic novelty reaffirm responsibilisation. Videos within our sample depict epigenetics as a new, important and relevant field. Audiences are urged to make active choices relating to epigenetic knowledge, out of both a responsibility to avoid detrimental impacts to oneself and others, and to realise personal and transgenerational benefits. However, the videos tend to omit qualifications of the promise and implications of epigenetics, nor do they signal the challenges of individual choice-making within unequal societies. Consequently, the popular YouTube videos in our sample serve to reproduce longstanding logics of responsibilisation even while insights from epigenetics are presented as novel, different and potentially empowering. Configurations of novelty can, then, be regarded as one means through which such dominant discourses are reaffirmed.