Identification of regulatory elements that control PPARγ expression in adipocyte progenitors.
Identification of regulatory elements that control PPARγ expression in adipocyte progenitors.
复制标题
DOI：
10.1371/journal.pone.0072511
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Saez E
中科院分区：
文献类型：
--
作者：
Chou WL;Galmozzi A;Partida D;Kwan K;Yeung H;Su AI;Saez E
脂肪组织的更新和肥胖驱动的脂肪细胞数量的扩张依赖于脂肪祖细胞的增殖和分化，这些祖细胞位于与脂肪库协调发展的脉管系统中。调控祖细胞向脂肪谱系转变的转录事件尚不清楚。由于核受体PPARγ的表达决定了脂肪谱系，分离脂肪前体中控制PPARγ表达的元件可能会发现早期脂肪细胞决定的转录调节因子。在这里，我们描述了在转基因小鼠中鉴定和验证了来自PPARγ位点的5个高度保守的非编码序列，这些序列可以以概括组织特异性PPARγ表达模式的方式驱动报告基因的表达。令人惊讶的是，这5种元素似乎可以控制与脂肪库脉管系统相关的脂肪细胞前体中的PPARγ表达，而不是在成熟脂肪细胞中。这5个PPARγ调控序列的特征可以分离与这些顺式元件结合的转录因子，并为正常和病理状态下脂肪组织扩张的分子调控提供见解。
Adipose tissue renewal and obesity-driven expansion of fat cell number are dependent on proliferation and differentiation of adipose progenitors that reside in the vasculature that develops in coordination with adipose depots. The transcriptional events that regulate commitment of progenitors to the adipose lineage are poorly understood. Because expression of the nuclear receptor PPARγ defines the adipose lineage, isolation of elements that control PPARγ expression in adipose precursors may lead to discovery of transcriptional regulators of early adipocyte determination. Here, we describe the identification and validation in transgenic mice of 5 highly conserved non-coding sequences from the PPARγ locus that can drive expression of a reporter gene in a manner that recapitulates the tissue-specific pattern of PPARγ expression. Surprisingly, these 5 elements appear to control PPARγ expression in adipocyte precursors that are associated with the vasculature of adipose depots, but not in mature adipocytes. Characterization of these five PPARγ regulatory sequences may enable isolation of the transcription factors that bind these cis elements and provide insight into the molecular regulation of adipose tissue expansion in normal and pathological states.
登录
查看更多内容
影响因子：
64.5
作者：
Rodeheffer, Matthew S.;Birsoy, Kivanc;Friedman, Jeffrey M.
通讯作者：
Friedman, Jeffrey M.
DOI：
10.1073/pnas.1010929108
发表时间：
2011-01-04
影响因子：
11.1
作者：
Schulz, Tim J.;Huang, Tian Lian;Tseng, Yu-Hua
通讯作者：
Tseng, Yu-Hua
影响因子：
4.8
作者：
Quach, Julie M.;Walker, Emma C.;Martin, T. John
通讯作者：
Martin, T. John
影响因子：
4.2
作者：
Cusi, Kenneth
通讯作者：
Cusi, Kenneth
影响因子：
64.5
作者：
Festa E;Fretz J;Berry R;Schmidt B;Rodeheffer M;Horowitz M;Horsley V
通讯作者：
Horsley V