β-actin contributes to open chromatin for activation of the adipogenic pioneer factor CEBPA during transcriptional reprograming

• Adipogenesis is regulated by a cascade of signals that drive transcriptional reprogramming in adipocytes. Here, we report that nuclear actin regulates the chromatin states that establish tissue- specific expression during adipogenesis. To study the role of beta-actin in adipocyte differentiation, we conducted RNA sequencing on wild-type and beta-actin knockout mouse embryonic fibroblasts (MEFs) after reprograming to adipocytes. We found that beta-actin depletion affects induction of several adipogenic genes during transcriptional reprograming. This impaired regulation of adipogenic genes is linked to reduced expression of the pioneer factor Cebpa and is rescued by reintroducing NLS-tagged beta-actin. ATAC-Seq in knockout MEFs revealed that actin-dependent reduction of Cebpa expression correlates with decreased chromatin accessibility and loss of chromatin association of the ATPase Brg1. This, in turn, impairs CEBPB's association with its Cebpa promoter-proximal binding site during adipogenesis. We propose a role for the nuclear beta-actin pool in maintaining open chromatin for transcriptional reprogramming during adipogenic differentiation.

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NATURVETENSKAP  -- Biologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences (hsv//eng)

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