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

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, nothin...

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Autores principales: Bina, Minou, Wyss, Phillip, Novorolsky, Elise, Zulkelfi, Noorfatin, Xue, Jing, Price, Randi, Fay, Matthew, Gutmann, Zach, Fogler, Brian, Wang, Daidong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3890651/
https://www.ncbi.nlm.nih.gov/pubmed/24373511
http://dx.doi.org/10.1186/1471-2164-14-927
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author Bina, Minou
Wyss, Phillip
Novorolsky, Elise
Zulkelfi, Noorfatin
Xue, Jing
Price, Randi
Fay, Matthew
Gutmann, Zach
Fogler, Brian
Wang, Daidong
author_facet Bina, Minou
Wyss, Phillip
Novorolsky, Elise
Zulkelfi, Noorfatin
Xue, Jing
Price, Randi
Fay, Matthew
Gutmann, Zach
Fogler, Brian
Wang, Daidong
author_sort Bina, Minou
collection PubMed
description 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.
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spelling pubmed-38906512014-01-15 Discovery of MLL1 binding units, their localization to CpG Islands, and their potential function in mitotic chromatin Bina, Minou Wyss, Phillip Novorolsky, Elise Zulkelfi, Noorfatin Xue, Jing Price, Randi Fay, Matthew Gutmann, Zach Fogler, Brian Wang, Daidong BMC Genomics Research Article 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. BioMed Central 2013-12-28 /pmc/articles/PMC3890651/ /pubmed/24373511 http://dx.doi.org/10.1186/1471-2164-14-927 Text en Copyright © 2013 Bina et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Bina, Minou
Wyss, Phillip
Novorolsky, Elise
Zulkelfi, Noorfatin
Xue, Jing
Price, Randi
Fay, Matthew
Gutmann, Zach
Fogler, Brian
Wang, Daidong
Discovery of MLL1 binding units, their localization to CpG Islands, and their potential function in mitotic chromatin
title Discovery of MLL1 binding units, their localization to CpG Islands, and their potential function in mitotic chromatin
title_full Discovery of MLL1 binding units, their localization to CpG Islands, and their potential function in mitotic chromatin
title_fullStr Discovery of MLL1 binding units, their localization to CpG Islands, and their potential function in mitotic chromatin
title_full_unstemmed Discovery of MLL1 binding units, their localization to CpG Islands, and their potential function in mitotic chromatin
title_short Discovery of MLL1 binding units, their localization to CpG Islands, and their potential function in mitotic chromatin
title_sort discovery of mll1 binding units, their localization to cpg islands, and their potential function in mitotic chromatin
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3890651/
https://www.ncbi.nlm.nih.gov/pubmed/24373511
http://dx.doi.org/10.1186/1471-2164-14-927
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