HOXC9 directly regulates distinct sets of genes to coordinate diverse cellular processes during neuronal differentiation.
HOXC9 directly regulates distinct sets of genes to coordinate diverse cellular processes during neuronal differentiation.
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HOXC9 直接调节不同的基因组以协调神经元分化过程中的不同细胞过程
DOI：
10.1186/1471-2164-14-830
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发表时间：
2013-11-25
期刊：
影响因子：
4.4
通讯作者：
Ding HF
中科院分区：
文献类型：
--
作者：
Wang X;Choi JH;Ding J;Yang L;Ngoka LC;Lee EJ;Zha Y;Mao L;Jin B;Ren M;Cowell J;Huang S;Shi H;Cui H;Ding HF
细胞分化的特征在于获得专门的结构和功能、细胞周期退出和DNA损伤反应的整体衰减。在分化过程中，这些不同的细胞事件如何在分子水平上协调，这在很大程度上是未知的。我们在HOXC 9诱导的神经母细胞瘤细胞分化的模型系统中解决了这个问题。我们对HOXC 9诱导的神经元分化程序进行了全基因组分析。微阵列基因表达谱显示，HOXC 9诱导的分化与2,370个基因的转录调控有关，其特征是神经元基因的整体上调和细胞周期和DNA修复基因的下调。值得注意的是，ChIP-seq的全基因组定位表明HOXC 9与这些基因中的40%结合，包括大量参与神经元分化，细胞周期进展和DNA损伤反应的基因。此外，我们发现HOXC 9与转录抑制因子E2 F6相互作用，并将其募集到细胞周期基因的启动子中，以抑制其表达。我们的研究结果表明，HOXC 9通过直接激活和抑制不同基因组的转录来协调与分化相关的多种细胞过程。
Cellular differentiation is characterized by the acquisition of specialized structures and functions, cell cycle exit, and global attenuation of the DNA damage response. It is largely unknown how these diverse cellular events are coordinated at the molecular level during differentiation. We addressed this question in a model system of neuroblastoma cell differentiation induced by HOXC9. We conducted a genome-wide analysis of the HOXC9-induced neuronal differentiation program. Microarray gene expression profiling revealed that HOXC9-induced differentiation was associated with transcriptional regulation of 2,370 genes, characterized by global upregulation of neuronal genes and downregulation of cell cycle and DNA repair genes. Remarkably, genome-wide mapping by ChIP-seq demonstrated that HOXC9 bound to 40% of these genes, including a large number of genes involved in neuronal differentiation, cell cycle progression and the DNA damage response. Moreover, we showed that HOXC9 interacted with the transcriptional repressor E2F6 and recruited it to the promoters of cell cycle genes for repressing their expression. Our results demonstrate that HOXC9 coordinates diverse cellular processes associated with differentiation by directly activating and repressing the transcription of distinct sets of genes.
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影响因子：
64.5
作者：
Duester G
通讯作者：
Duester G
影响因子：
64.5
作者：
Dasen, Jeremy S.;De Camilli, Alessandro;Jessell, Thomas M.
通讯作者：
Jessell, Thomas M.
影响因子：
64.8
作者：
Dasen, JS;Liu, JP;Jessell, TM
通讯作者：
Jessell, TM
影响因子：
12.4
作者：
Eramo, A.;Ricci-Vitiani, L.;De Maria, R.
通讯作者：
De Maria, R.
DOI：
10.1016/s0006-291x(75)80444-x
发表时间：
1975-01-01
影响因子：
3.1
作者：
BYFIELD, JE;LEE, YC;FINKLESTEIN, JZ
通讯作者：
FINKLESTEIN, JZ