Association of the transcriptional corepressor TIF1β with heterochromatin protein 1 (HP1):: an essential role for progression through differentiation
Association of the transcriptional corepressor TIF1β with heterochromatin protein 1 (HP1):: an essential role for progression through differentiation
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DOI：
10.1101/gad.302904
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发表时间：
2004-09-01
影响因子：
10.5
通讯作者：
Losson, R
中科院分区：
文献类型：
--
作者：
Cammas, F;Herzog, M;Losson, R
转录中介因子1 β（TIF 1 β）是含KRAB结构域的锌指蛋白的辅阻遏物，并被认为通过与染色质重塑和组蛋白修饰活性以及异染色质蛋白1（HP 1）蛋白的募集相关来调节特定位点的染色质组织，从而在细胞生理学中发挥重要作用。在这项研究中，我们设计了一个修饰的胚胎癌F9细胞系（TIF 1 β（HP 1box/-）），表达突变的TIF 1 β蛋白（TIF 1 β（HP 1box/-）），不能与FIN蛋白相互作用。TIF 1 β（HP 1box/-）和TIF 1 β（+/-）细胞的表型分析显示，TIF 1 β-HP 1相互作用对于在视黄酸（RA）处理下F9细胞分化成原始内胚层样（PrE）细胞不是必需的，但是对于在添加cAMP时进一步分化成壁内胚层样（PE）细胞和对于在用RA处理囊泡时分化成内脏内胚层样细胞是必需的。互补实验表明，TIF 1 β-HP 1相互作用仅在早期分化的PrE细胞内的短时间窗口内是必需的，以建立选择性可传递的能力，从而在进一步的cAMP诱导信号下终末分化。此外，在PrE分化过程中，与野生型细胞相比，TIF 1 β（HP 1box/-）细胞中三个内胚层特异性基因GATA 6、HNF 4和Dab 2的表达下调。总的来说，这些数据表明，TIF 1 β和HP 1蛋白之间的相互作用是通过调节内胚层分化的主要参与者的表达，通过分化的进展是必不可少的。
The transcriptional intermediary factor 1beta (TIF1beta) is a corepressor for KRAB-domain-containing zinc finger proteins and is believed to play essential roles in cell physiology by regulating chromatin organization at specific loci through association with chromatin remodeling and histone-modifying activities and recruitment of heterochromatin protein 1 (HP1) proteins. In this study, we have engineered a modified embryonal carcinoma F9 cell line (TIF1beta(HP1box/-)) expressing a mutated TIF1beta protein (TIF1beta(HP1box/-)) unable to interact with FIN proteins. Phenotypic analysis of TIF1beta(HP1box/-) and TIF1beta(+/-) cells shows that TIF1beta-HP1 interaction is not required for differentiation of F9 cells into primitive endoderm-like (PrE) cells on retinoic acid (RA) treatment but is essential for further differentiation into parietal endoderm-like (PE) cells on addition of cAMP and for differentiation into visceral endoderm-like cells on treatment of vesicles with RA. Complementation experiments reveal that TIF1beta-HP1 interaction is essential only during a short window of time within early differentiating PrE cells to establish a selective transmittable competence to terminally differentiate on further cAMP inducing signal. Moreover, the expression of three endoderm-specific genes, GATA6, HNF4, and Dab2, is down-regulated in TIF1beta(HP1box/-) cells compared with wild-type cells during PrE differentiation. Collectively, these data demonstrate that the interaction between TIF1beta and HP1 proteins is essential for progression through differentiation by regulating the expression of endoderm differentiation master players.