Discovery of MLL1 binding units, their localization to CpG Islands, and their potential function in mitotic chromatin

BMC Genomics

Research Article

Noorfatin Zulkelfi¹  Zach Gutmann¹  Brian Fogler¹  Jing Xue¹  Phillip Wyss¹  Daidong Wang¹  Elise Novorolsky¹  Minou Bina¹  Randi Price¹  Matthew Fay¹ 

[1] Department of Chemistry, Purdue University, 47907, West Lafayette, IN, USA;

关键词: Cis;    Chromatin structure;    Codes in DNA;    CGG repeats;    CpG islands;    FMR1;    HOXA;    HOXB;    HOXC;    HOXD;    MLL;    MLL1;    Gene bookmarking;    Gene regulation;    Human genome;    Mammalian genomes;    Regulatory codes;    Trithorax response elements;    TREs;    Mitosis;    Cell division;   

DOI  :  10.1186/1471-2164-14-927

 received in 2013-08-02, accepted in 2013-12-16,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundMixed 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.ResultsBy 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.ConclusionOur 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.

【 授权许可】

CC BY   
© Bina et al.; licensee BioMed Central Ltd. 2013