High-resolution profiling of the LEDGF/p75 chromatin interaction in the ENCODE region.
High-resolution profiling of the LEDGF/p75 chromatin interaction in the ENCODE region.
复制标题
DOI：
10.1093/nar/gkq410
复制
发表时间：
2010-10
影响因子：
14.9
通讯作者：
Gijsbers R
中科院分区：
文献类型：
--
作者：
De Rijck J;Bartholomeeusen K;Ceulemans H;Debyser Z;Gijsbers R
透镜上皮衍生生长因子/p75（LEDGF/p75）是一种转录辅激活因子，参与应激反应、自身免疫性疾病、癌症和HIV复制。核孔蛋白NUP 98和LEDGF/p75之间的融合已在人类急性和慢性髓性白血病中发现，并且LEDGF/p75与混合谱系白血病（MLL）/menin的关联对于白血病转化是关键的。在慢病毒复制过程中，LEDGF/p75将整合前复合物束缚在宿主染色质上，导致整合到活性转录单位（TU）中的偏好。LEDGF/p75的共有功能是将货物拴系到染色质。在这方面，我们确定了LEDGF/p75染色质结合谱。为此，我们使用DamID技术，并专注于高度注释的ENCODE（DNA元件百科全书）区域。LEDGF/p75主要结合活性TU的转录起始位点的下游，与这些位置处的HIV-1整合位点的富集一致。我们表明，LEDGF/p75的结合并不局限于基因组中的应激反应元件，与200多个基因组特征的相关性分析揭示了与活性染色质标记物的关联，如H3和H4乙酰化，H3 K4单甲基化和RNA聚合酶II结合。有趣的是，一些关联与HIV-1整合无关，表明并非染色体上的所有LEDGF/p75复合物都适合HIV-1整合。
Lens epithelium-derived growth factor/p75 (LEDGF/p75) is a transcriptional coactivator involved in stress response, autoimmune disease, cancer and HIV replication. A fusion between the nuclear pore protein NUP98 and LEDGF/p75 has been found in human acute and chronic myeloid leukemia and association of LEDGF/p75 with mixed-lineage leukemia (MLL)/menin is critical for leukemic transformation. During lentiviral replication, LEDGF/p75 tethers the pre-integration complex to the host chromatin resulting in a bias of integration into active transcription units (TUs). The consensus function of LEDGF/p75 is tethering of cargos to chromatin. In this regard, we determined the LEDGF/p75 chromatin binding profile. To this purpose, we used DamID technology and focused on the highly annotated ENCODE (Encyclopedia of DNA Elements) regions. LEDGF/p75 primarily binds downstream of the transcription start site of active TUs in agreement with the enrichment of HIV-1 integration sites at these locations. We show that LEDGF/p75 binding is not restricted to stress response elements in the genome, and correlation analysis with more than 200 genomic features revealed an association with active chromatin markers, such as H3 and H4 acetylation, H3K4 monomethylation and RNA polymerase II binding. Interestingly, some associations did not correlate with HIV-1 integration indicating that not all LEDGF/p75 complexes on the chromosome are amenable to HIV-1 integration.
登录
查看更多内容
影响因子：
4.8
作者：
Cherepanov, P;Maertens, G;Debyser, Z
通讯作者：
Debyser, Z
影响因子：
4.8
作者：
Busschots, K;Vercammen, J;Debyser, Z
通讯作者：
Debyser, Z
影响因子：
11.4
作者：
Ge, H;Si, YZ;Roeder, RG
通讯作者：
Roeder, RG
影响因子：
13.6
作者：
Ganapathy, V;Daniels, T;Casiano, CA
通讯作者：
Casiano, CA
影响因子：
4.8
作者：
Cherepanov, P;Devroe, E;Engelman, A
通讯作者：
Engelman, A