Discovery of MLL1 binding units, their localization to CpG Islands, and their potential function in mitotic chromatin.
Discovery of MLL1 binding units, their localization to CpG Islands, and their potential function in mitotic chromatin.
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发现MLL1结合单元，其定位到CpG岛，以及它们在有丝分裂染色质中的潜在功能。
DOI：
10.1186/1471-2164-14-927
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发表时间：
2013-12-28
期刊：
影响因子：
4.4
通讯作者：
Wang D
中科院分区：
文献类型：
--
作者：
Bina M;Wyss P;Novorolsky E;Zulkelfi N;Xue J;Price R;Fay M;Gutmann Z;Fogler B;Wang D
混合谱系白血病 1 (MLL1) 是果蝇 Trithorax 的哺乳动物直系同源物。在果蝇中，Trithorax 复合体通过与 Trithorax 响应元件 (TRE) 的相互作用将活性基因的记忆传递给子细胞。然而，尽管它们的功能很重要，但我们对哺乳动物基因组 DNA 中可能充当 TRE 的序列特征一无所知。通过分析报道的 DNA 结合测定结果，我们确定了几个富含 CpG 的基序作为潜在的 MLL1 结合单位（定义为语素）。我们发现这些语素分散在相对较大的人类启动子序列集合中，并且密集地出现在蛋白质编码基因的转录起始位点附近。全基因组分析对 CpG 岛局部频繁出现的语素进行分析。在人类 HOX 基因座中，语素分布在 CpG 岛屿上，在某些情况下尾部延伸到岛屿周围的海岸和架子上。通过分析染色质免疫沉淀测定的结果，我们发现了据报道与 MLL1 相关的语素出现、CpG 岛和染色质片段之间的联系。此外，我们发现染色质中报告的 MLL1 驱动的“书签”区域与 CpG 岛中 MLL1 语素的频繁出现存在对应关系。我们的结果表明 MLL1 语素与定义哺乳动物 TRE 的序列特征有关，并为 CpG 岛提供了新的功能。显然，我们的研究结果为哺乳动物基因组 DNA 中存在潜在 TRE 提供了第一个证据，并为 CpG 岛与 MLL1 的基因书签之间的联系提供了第一个证据，以在有丝分裂期间传递高度活跃基因的记忆。我们的结果进一步表明重叠语素在基因组 DNA 中产生紧密堆积的多个 MLL1 结合事件中的作用，以便 MLL1 分子可以相互作用并同时驻留在人类染色体中扩展的潜在转录维持元件上，以在有丝分裂期间传递高度活跃基因的记忆。
Mixed Lineage Leukemia 1 (MLL1) is a mammalian ortholog of the Drosophila Trithorax. In Drosophila, Trithorax complexes transmit the memory of active genes to daughter cells through interactions with Trithorax Response Elements (TREs). However, despite their functional importance, nothing is known about sequence features that may act as TREs in mammalian genomic DNA. By analyzing results of reported DNA binding assays, we identified several CpG rich motifs as potential MLL1 binding units (defined as morphemes). We find that these morphemes are dispersed within a relatively large collection of human promoter sequences and appear densely packed near transcription start sites of protein-coding genes. Genome wide analyses localized frequent morpheme occurrences to CpG islands. In the human HOX loci, the morphemes are spread across CpG islands and in some cases tail into the surrounding shores and shelves of the islands. By analyzing results of chromatin immunoprecipitation assays, we found a connection between morpheme occurrences, CpG islands, and chromatin segments reported to be associated with MLL1. Furthermore, we found a correspondence of reported MLL1-driven “bookmarked” regions in chromatin to frequent occurrences of MLL1 morphemes in CpG islands. Our results implicate the MLL1 morphemes in sequence-features that define the mammalian TREs and provide a novel function for CpG islands. Apparently, our findings offer the first evidence for existence of potential TREs in mammalian genomic DNA and the first evidence for a connection between CpG islands and gene-bookmarking by MLL1 to transmit the memory of highly active genes during mitosis. Our results further suggest a role for overlapping morphemes in producing closely packed and multiple MLL1 binding events in genomic DNA so that MLL1 molecules could interact and reside simultaneously on extended potential transcriptional maintenance elements in human chromosomes to transmit the memory of highly active genes during mitosis.
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影响因子：
4.8
作者：
Cherepanov, P;Maertens, G;Debyser, Z
通讯作者：
Debyser, Z
DOI：
10.1111/j.1742-4658.2010.07609.x
发表时间：
2010-04
期刊：
The FEBS journal
影响因子：
--
作者：
Cosgrove MS;Patel A
通讯作者：
Patel A
影响因子：
14.9
作者：
Chatr-Aryamontri A;Breitkreutz BJ;Heinicke S;Boucher L;Winter A;Stark C;Nixon J;Ramage L;Kolas N;O'Donnell L;Reguly T;Breitkreutz A;Sellam A;Chen D;Chang C;Rust J;Livstone M;Oughtred R;Dolinski K;Tyers M
通讯作者：
Tyers M
影响因子：
64.5
作者：
FU, YH;KUHL, DPA;CASKEY, CT
通讯作者：
CASKEY, CT
影响因子：
11.5
作者：
Chase, Andrew;Cross, Nicholas C. P.
通讯作者：
Cross, Nicholas C. P.