Chromatin profiling of dREAM and dNuRD complexes

dREAM 和 dNuRD 复合物的染色质分析

• 批准号: 37884923
• 负责人: Professor Dr. Alexander Brehm
• 金额: --
• 依托单位: Institut für Molekularbiologie und Tumorforschung (IMT)
• 依托单位国家: 德国
• 项目类别: Research Units
• 财政年份: 2007
• 资助国家: 德国
• 起止时间: 2006-12-31 至 2009-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/37884923?language=en
• 关键词: Chromatin; profiling; dREAM; dNuRD; complexes

Regulation of chromatin structure is of fundamental importance during differentiation, proliferation and malignant transformation of cells. Several chromatin regulating protein complexes have been identified but we know little about how they cooperate. dREAM and dNuRD are highly conserved multisubunit protein complexes. Human homologs of dREAM and dNuRD subunits, such as the Retinoblastoma tumour suppressor pRb and the metastasis- associated proteins MTA1-3, are deregulated in cancer. In C.elegans both complexes cooperate to regulate cell fate determination during development. Both, dREAM and dNuRD are thought to repress transcription by acting on chromatin structure. Here, we propose to use novel microarray based methods (ChlP-on-chip, DamID, RNAi/microarray) to determine genome wide binding patterns and target genes of dREAM and dNuRD. We aim to identify and characterize genes coregulated by both complexes and to reveal the role of histone modification patterns in dREAM and dNuRD mediated gene repression. With this systems biology approach, we are hoping to learn how the action of different chromatin regulating complexes is orchestrated to effect the precise execution of transcriptional programmes during the development of multicellular organisms.

染色质结构的调节在细胞的分化、增殖和恶性转化过程中具有根本的重要性。一些染色质调节蛋白复合物已被确定，但我们知道他们如何合作。dREAM和dNuRD是高度保守的多亚基蛋白复合物。dREAM和dNuRD亚基的人类同源物，如视网膜母细胞瘤肿瘤抑制因子pRb和转移相关蛋白MTA 1 -3，在癌症中被失调。在秀丽隐杆线虫中，这两种复合物在发育过程中共同调节细胞命运的决定。dREAM和dNuRD都被认为通过作用于染色质结构来抑制转录。在这里，我们提出使用新的基于微阵列的方法（ChIP芯片，DamID，RNAi/微阵列）来确定全基因组范围的结合模式和dREAM和dNuRD的靶基因。我们的目的是确定和表征基因的共同调控的两个复合物，并揭示组蛋白修饰模式的作用，dREAM和dNuRD介导的基因抑制。通过这种系统生物学方法，我们希望了解不同染色质调节复合物的作用是如何协调的，以影响多细胞生物体发育过程中转录程序的精确执行。