Heritable, Allele-Specific Chromosomal Looping between Tandem Promoters Specifies Promoter Usage of SHC1
Heritable, Allele-Specific Chromosomal Looping between Tandem Promoters Specifies Promoter Usage of SHC1
复制标题
串联启动子之间的可遗传、等位基因特异性染色体环指定了 SHC1 的启动子使用
DOI：
10.1128/mcb.00658-17
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发表时间：
2018-02
影响因子：
5.3
通讯作者：
Liu Z
中科院分区：
文献类型：
--
作者：
Li X;Lin Z;Wang H;Zhao D;Xu X;Wei Y;Li X;Li X;Xiang Y;Terada LS;Liu Z
人类基因组中有一半的基因含有可选择的启动子，其中一些启动子产生具有相反功能的产物。这种替代启动子的异常沉默或激活与多种疾病相关，包括癌症，但关于控制替代启动子选择的分子机制知之甚少。SHC 1基因编码p46 Shc/p52 Shc和p66 Shc，这两种蛋白质分别通过SHC 1上游和下游串联启动子启动的转录产生，反向调节锚定非依赖性生长。在这里，我们证明了这些启动子的激活是相互排斥的单独的等位基因在单一的初级内皮细胞在一个可遗传的方式，确保两个转录的细胞表达。不转录p66 Shc的外周血淋巴细胞双等位基因地转录p52 Shc。这种独特的单等位基因转录模式是通过串联启动子之间的等位基因特异性染色体成环建立的，其使上游启动子沉默。我们的研究结果揭示了一个新的机制，通过更高层次的染色质结构来控制替代启动子的使用。
ABSTRACT One-half of the genes in the human genome contain alternative promoters, some of which generate products with opposing functions. Aberrant silencing or activation of such alternative promoters is associated with multiple diseases, including cancer, but little is known regarding the molecular mechanisms that control alternative promoter choice. The SHC1 gene encodes p46Shc/p52Shc and p66Shc, proteins oppositely regulating anchorage-independent growth that are produced by transcription initiated from the upstream and downstream tandem promoters of SHC1, respectively. Here we demonstrate that activation of these promoters is mutually exclusive on separate alleles in single primary endothelial cells in a heritable fashion, ensuring expression of both transcripts by the cell. Peripheral blood lymphocytes that do not transcribe p66Shc transcribed p52Shc biallelically. This distinct monoallelic transcription pattern is established by allele-specific chromosomal looping between tandem promoters, which silences the upstream promoter. Our results reveal a new mechanism to control alternative promoter usage through higher-order chromatin structure.
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影响因子：
30.8
作者：
Schoenfelder S;Sugar R;Dimond A;Javierre BM;Armstrong H;Mifsud B;Dimitrova E;Matheson L;Tavares-Cadete F;Furlan-Magaril M;Segonds-Pichon A;Jurkowski W;Wingett SW;Tabbada K;Andrews S;Herman B;LeProust E;Osborne CS;Koseki H;Fraser P;Luscombe NM;Elderkin S
通讯作者：
Elderkin S
影响因子：
64.5
作者：
Giorgio, M;Migliaccio, E;Pelicci, PG
通讯作者：
Pelicci, PG
影响因子：
8
作者：
Ma, Z.;Liu, Z.;Wu, R-F;Terada, L. S.
通讯作者：
Terada, L. S.
影响因子：
32.4
作者：
Guo, LY;Hu-Li, J;Paul, WE
通讯作者：
Paul, WE
影响因子：
10.5
作者：
HENDERSON, SL;RYAN, K;SOLLNERWEBB, B
通讯作者：
SOLLNERWEBB, B