E-MTAB-6995
RNA-seq of ZFP30 knock-down and knock-out in mouse 3T3-L1 and IBA cells during adipogenic differentiation
We show that a hitherto poorly characterized KRAB domain-containing zinc-finger (ZF) transcription factor, ZFP30, positively regulates adipogenesis. We demonstrate ZFP30's function in murine in vitro and in vivo models, as well as in human stromal vascular fraction cells. We reveal through mechanistic studies that ZFP30 directly targets and activates Pparg2 by binding a retrotransposon-derived enhancer, suggesting a process of adipogenic exaptation. We further show that ZFP30 recruits the co-regulator KRAB-associated protein 1 (KAP1), which, surprisingly, acts as a ZFP30 co-activator in this adipogenic context. We show that a hitherto poorly characterized KRAB domain-containing zinc-finger (ZF) transcription factor, ZFP30, positively regulates adipogenesis. We demonstrate ZFP30's function in murine in vitro and in vivo models, as well as in human stromal vascular fraction cells. To globally characterize ZFP30's target landscape, we performed transcriptomic analyses after Zfp30 reduction or absence, in 3T3-L1 and in IBA cells, respectively. As we already observed significant (p<0.01, t-test) reduction in adipogenic marker gene expression in Zfp30 KD samples after two days of adipogenic induction, we included day 0 and day 2 measurements in both 3T3-L1 and IBA cells, and two additional time-points (2 hours and day 4) in IBA cells.
We show that a hitherto poorly characterized KRAB domain-containing zinc-finger (ZF) transcription factor, ZFP30, positively regulates adipogenesis. We demonstrate ZFP30's function in murine in vitro and in vivo models, as well as in human stromal vascular fraction cells. We reveal through mechanistic studies that ZFP30 directly targets and activates Pparg2 by binding a retrotransposon-derived enhancer, suggesting a process of adipogenic exaptation. We further show that ZFP30 recruits the co-regulator KRAB-associated protein 1 (KAP1), which, surprisingly, acts as a ZFP30 co-activator in this adipogenic context. We show that a hitherto poorly characterized KRAB domain-containing zinc-finger (ZF) transcription factor, ZFP30, positively regulates adipogenesis. We demonstrate ZFP30's function in murine in vitro and in vivo models, as well as in human stromal vascular fraction cells. To globally characterize ZFP30's target landscape, we performed transcriptomic analyses after Zfp30 reduction or absence, in 3T3-L1 and in IBA cells, respectively. As we already observed significant (p<0.01, t-test) reduction in adipogenic marker gene expression in Zfp30 KD samples after two days of adipogenic induction, we included day 0 and day 2 measurements in both 3T3-L1 and IBA cells, and two additional time-points (2 hours and day 4) in IBA cells.