Genomic occupancy of HLH, AP1 and Runx2 motifs within a nuclease sensitive site of the Runx2 gene.
Genomic occupancy of HLH, AP1 and Runx2 motifs within a nuclease sensitive site of the Runx2 gene.
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DOI：
10.1002/jcp.22109
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发表时间：
2013-02
影响因子：
5.6
通讯作者：
van Wijnen, Andre J.
中科院分区：
文献类型：
--
作者：
Hovhannisyan, Hayk;Zhang, Ying;Hassan, Mohammad Q.;Wu, Hai;Glackin, Carlotta;Lian, Jane B.;Stein, Janet L.;Montecino, Martin;Stein, Gary S.;van Wijnen, Andre J.
调节Runt相关转录因子Runx 2表达的表观遗传机制对于控制骨骼发育过程中的成骨活性至关重要。在这里，我们通过基因组DNA酶I足迹法和染色质免疫沉淀法（ChIP）鉴定了成骨细胞中内源性骨相关Runx 2启动子（P1）120 kbp内的真正调控元件。我们确定了一个跨越P1启动子的约10 kbp的基因组结构域，该结构域与乙酰化组蛋白H3和H4相互作用，反映了MC 3 T3成骨细胞中开放的染色质构象。这个大的染色质结构域包含一个单一的主要DNaseI超敏感（DHS）区域，定义了一个0.4 kbp的“基础核心”启动子。该区域包括两个内源基因组蛋白/DNA相互作用位点（即，在活化蛋白1 [AP 1]、E-box和Runx基序处的足迹）。螺旋环受阻（HLH）/E盒占用和DHS区域的存在持续存在于几种间充质细胞类型，但AP 1位点占用只发生在S期Runx 2表达最小时。HLH/E盒的点突变显著降低了基础启动子活性。我们的研究结果表明，Runx 2 P1启动子利用两个稳定的主要蛋白质/DNA相互作用域与AP 1和HLH因子。这些网站的功能与动态和发育反应的网站在一个主要的DHS区域支持骨特异性转录的表观遗传控制时，成骨细胞过渡到静止或分化状态。
Epigenetic mechanisms mediating expression of the Runt-related transcription factor Runx2 are critical for controlling its osteogenic activity during skeletal development. Here, we characterized bona fide regulatory elements within 120 kbp of the endogenous bone-related Runx2 promoter (P1) in osteoblasts by genomic DNase I footprinting and chromatin immunoprecipitations (ChIPs). We identified a ~10 kbp genomic domain spanning the P1 promoter that interacts with acetylated histones H3 and H4 reflecting an open chromatin conformation in MC3T3 osteoblasts. This large chromatin domain contains a single major DNaseI hypersensitive (DHS) region that defines a 0.4 kbp “basal core” promoter. This region encompasses two endogenous genomic protein/DNA interaction sites (i.e., footprints at Activating Protein 1 [AP1], E-box and Runx motifs). Helix-Loop-Helix (HLH)/E-box occupancy and presence of the DHS region persists in several mesenchymal cell types, but AP1 site occupancy occurs only during S phase when Runx2 expression is minimal. Point-mutation of the HLH/E box dramatically reduces basal promoter activity. Our results indicate that the Runx2 P1 promoter utilizes two stable principal protein/DNA interaction domains associated with AP1 and HLH factors. These sites function together with dynamic and developmentally responsive sites in a major DHS region to support epigenetic control of bone-specific transcription when osteoblasts transition into a quiescent or differentiated state.
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影响因子：
5.6
作者：
Henriquez, Berta;Hepp, Matias;Merino, Paola;Sepulveda, Hugo;Van Wijnen, Andre J.;Lian, Jane B.;Stein, Gary S.;Stein, Janet L.;Montecino, Martin
通讯作者：
Montecino, Martin
影响因子：
3.7
作者：
Drissi, H;Pouliot, A;van Wijnen, AJ
通讯作者：
van Wijnen, AJ
影响因子：
5.3
作者：
Hassan, Mohammad Q.;Tare, Rahul;Lian, Jane B.
通讯作者：
Lian, Jane B.
DOI：
10.1615/critreveukargeneexpr.v18.i2.50
发表时间：
2008-01-01
影响因子：
1.6
作者：
Montecino, Martin;Stein, Gary S.;Arriagada, Gloria
通讯作者：
Arriagada, Gloria
影响因子：
4.2
作者：
Lee, Hee-Jung;Koh, Jung-Min;Lee, Jong-Young
通讯作者：
Lee, Jong-Young