Brahma is essential for Drosophila intestinal stem cell proliferation and regulated by Hippo signaling.
Brahma is essential for Drosophila intestinal stem cell proliferation and regulated by Hippo signaling.
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Brahma 对于果蝇肠道干细胞增殖至关重要，并受 Hippo 信号传导调节
DOI：
10.7554/elife.00999
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发表时间：
2013-10-15
期刊：
影响因子：
7.7
通讯作者：
Zhang L
中科院分区：
文献类型：
--
作者：
Jin Y;Xu J;Yin MX;Lu Y;Hu L;Li P;Zhang P;Yuan Z;Ho MS;Ji H;Zhao Y;Zhang L
染色质重塑过程是控制细胞增殖和再生的重要调控机制之一。果蝇肠道干细胞(ISCs)具有自我更新潜能，维持组织内环境平衡，是研究细胞生长和再生的良好模型。在这项研究中，我们证明了Brahma(BRM)染色质重塑复合体是ISC增殖和损伤诱导的中肠再生所必需的，并具有谱系特异性。间质干细胞和肠母细胞表达高水平的BRM蛋白；如果没有BRM，ISC的增殖和分化就会受到损害。重要的是，BRM复合体参与了扇贝-约克转录复合体诱导的ISC增殖，河马(HPO)信号通路通过诱导依赖于caspase的BRM切割来调节BRM蛋白水平，从而直接限制ISC的增殖。抗切割BRM蛋白促进ISC增殖。我们的发现强调了Hpo信号在调节表观遗传成分(如BRM)以控制下游转录从而控制ISC增殖方面的重要性。DOI：http://dx.doi.org/10.7554/eLife.00999.001
Chromatin remodeling processes are among the most important regulatory mechanisms in controlling cell proliferation and regeneration. Drosophila intestinal stem cells (ISCs) exhibit self-renewal potentials, maintain tissue homeostasis, and serve as an excellent model for studying cell growth and regeneration. In this study, we show that Brahma (Brm) chromatin-remodeling complex is required for ISC proliferation and damage-induced midgut regeneration in a lineage-specific manner. ISCs and enteroblasts exhibit high levels of Brm proteins; and without Brm, ISC proliferation and differentiation are impaired. Importantly, the Brm complex participates in ISC proliferation induced by the Scalloped–Yorkie transcriptional complex and that the Hippo (Hpo) signaling pathway directly restricted ISC proliferation by regulating Brm protein levels by inducing caspase-dependent cleavage of Brm. The cleavage resistant form of Brm protein promoted ISC proliferation. Our findings highlighted the importance of Hpo signaling in regulating epigenetic components such as Brm to control downstream transcription and hence ISC proliferation. DOI: http://dx.doi.org/10.7554/eLife.00999.001