Data from: Identification of ZEB1 as a central component of the adipogenic gene regulatory network

Adipose tissue is a key determinant of whole body metabolism and energy
homeostasis. Unraveling the regulatory mechanisms underlying adipogenesis
is therefore highly relevant from a biomedical perspective. Our current
understanding of fat cell differentiation is centered on the
transcriptional cascades driven by the C/EBP protein family and the master
regulator PPARγ. To elucidate further components of the adipogenic gene
regulatory network, we performed a large-scale transcription factor (TF)
screen overexpressing 734 TFs in mouse pre-adipocytes and probed their
effect on differentiation. We identified 23 novel pro-adipogenic TFs and
characterized the top ranking TF, ZEB1, as being essential for
adipogenesis both in vitro and in vivo. Moreover, its expression levels
correlate with fat cell differentiation potential in humans. Genomic
profiling further revealed that this TF directly targets and controls the
expression of most early and late adipogenic regulators, identifying ZEB1
as a central transcriptional component of fat cell differentiation.

脂肪组织（Adipose tissue）是决定全身代谢与能量稳态的关键组织。因此，解析脂肪生成（adipogenesis）的调控机制，具有重要的生物医学研究价值。目前我们对脂肪细胞分化的认知，主要聚焦于由C/EBP蛋白家族（C/EBP protein family）与核心调控因子过氧化物酶体增殖物激活受体γ（PPARγ）介导的转录级联反应。为进一步阐明脂肪生成基因调控网络的未知组分，我们开展了大规模转录因子（TF）筛选实验：在小鼠前脂肪细胞中过表达734种转录因子，并检测其对脂肪细胞分化的影响。我们共鉴定出23个全新的促脂肪生成转录因子，并对筛选排名首位的锌指E盒结合同源框1（ZEB1）展开功能表征，证实其在体外与体内环境下均为脂肪生成所必需。此外，ZEB1的表达水平与人类脂肪细胞的分化潜能呈显著正相关。基因组谱分析（Genomic profiling）进一步显示，该转录因子可直接靶向并调控绝大多数早期与晚期脂肪生成调控因子的表达，从而确定ZEB1是脂肪细胞分化过程中的核心转录调控组分。