...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular and Cellular Biology >The Super Elongation Complex Family of RNA Polymerase II Elongation Factors: Gene Target Specificity and Transcriptional Output
【24h】

The Super Elongation Complex Family of RNA Polymerase II Elongation Factors: Gene Target Specificity and Transcriptional Output

机译：RNA聚合酶II延伸因子的超级延伸复杂家族：基因靶标特异性和转录输出。

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The elongation stage of transcription is highly regulated in metazoans. We previously purified the AFF1- and AFF4-containing super elongation complex (SEC) as a major regulator of development and cancer pathogenesis. Here, we report the biochemical isolation of SEC-like 2 (SEC-L2) and SEC-like 3 (SEC-L3) containing AFF2 and AFF3 in association with P-TEFb, ENL/MLLT1, and AF9/MLLT3. The SEC family members demonstrate high levels of polymerase II (Pol II) C-terminal domain kinase activity; however, only SEC is required for the proper induction of the HSP70 gene upon stress. Genome-wide mRNA-Seq analyses demonstrated that SEC-L2 and SEC-L3 control the expression of different subsets of genes, while AFF4/SEC plays a more dominant role in rapid transcriptional induction in cells. MYC is one of the direct targets of AFF4/SEC, and SEC recruitment to the MYC gene regulates its expression in different cancer cells, including those in acute myeloid or lymphoid leukemia. These findings suggest that AFF4/SEC could be a potential therapeutic target for the treatment of leukemia or other cancers associated with MYC overexpression.
机译：转录的延伸阶段在后生动物中受到高度调节。我们先前纯化了含有AFF1和AFF4的超伸长复合物（SEC），将其作为发展和癌症发病机理的主要调节剂。在这里，我们报告生化分离的SEC样2（SEC-L2）和SEC样3（SEC-L3）包含与P-TEFb，ENL / MLLT1和AF9 / MLLT3关联的AFF2和AFF3。 SEC家族成员证明了高水平的聚合酶II（Pol II）C末端域激酶活性;然而，仅需SEC即可在压力下正确诱导 HSP70 基因。全基因组的mRNA-Seq分析表明SEC-L2和SEC-L3控制着不同基因子集的表达，而AFF4 / SEC在细胞的快速转录诱导中起着更主要的作用。 MYC 是AFF4 / SEC的直接靶标之一，SEC募集到 MYC 基因可调节其在不同癌细胞（包括急性髓样或淋巴白血病）中的表达。这些发现表明，AFF4 / SEC可能是治疗白血病或与 MYC 过表达相关的其他癌症的潜在治疗靶标。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号