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BMC Genomics

, 14:927

Human and rodent genomics


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.

KeywordsCis-elements 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 AbbreviationsCGIsCpG islands

H3K4Lysine 4 on histone H3

PcGPolycomb group

POLIIRNA polymerase II

PRC1Polycomb repressive complexes 1

PRC2Polycomb repressive complexes 2

PREsPolycomb response elements

TREsTrithorax response elements

TSSsTranscription start sites

TrxGTrithorax group

UCSCUniversity of California Santa Cruz.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2164-14-927 contains supplementary material, which is available to authorized users.

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Autor: Minou Bina - Phillip Wyss - Elise Novorolsky - Noorfatin Zulkelfi - Jing Xue - Randi Price - Matthew Fay - Zach Gutmann -


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