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首页> 外文期刊>BMC Genomics >Discovery of MLL1 binding units, their localization to CpG Islands, and their potential function in mitotic chromatin
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Discovery of MLL1 binding units, their localization to CpG Islands, and their potential function in mitotic chromatin

机译：MLL1结合单元的发现，它们在CpG岛的定位及其在有丝分裂染色质中的潜在功能

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Background 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. Results 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. Conclusion 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.
机译：背景混合谱系白血病1（MLL1）是果蝇Trihororax的哺乳动物直系同源物。在果蝇中，Trithorax复合体通过与Trithorax Response Elements（TRE）的相互作用将活性基因的记忆传递给子细胞。然而，尽管它们具有功能重要性，但对于可能在哺乳动物基因组DNA中充当TRE的序列特征一无所知。结果通过分析已报道的DNA结合测定的结果，我们鉴定了几个富含CpG的基序作为潜在的MLL1结合单位（定义为语素）。我们发现这些词素分散在相对较大的人类启动子序列集合中，并密集地堆积在蛋白质编码基因的转录起始位点附近。全基因组范围分析局部频繁的语素发生到CpG岛。在人类HOX基因座中，这些语素分布在CpG岛上，在某些情况下，尾巴进入岛的周围海岸和架子。通过分析染色质免疫沉淀分析的结果，我们发现词素出现，CpG岛和据报道与MLL1相关的染色质片段之间存在联系。此外，我们发现染色质中报道的MLL1驱动的“标记”区域与CpG岛中MLL1词素的频繁发生对应。结论我们的结果暗示了MLL1语素的序列特征可定义哺乳动物TRE，并为CpG岛提供新功能。显然，我们的发现为哺乳动物基因组DNA中潜在TRE的存在提供了第一个证据，也为CpG岛与MLL1的基因标记功能之间的联系提供了第一个证据，以在有丝分裂过程中传递高活性基因的记忆。我们的结果进一步表明重叠的语素在基因组DNA中产生紧密堆积的多重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，从而在有丝分裂过程中传递高活性基因的记忆。

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