ALL-1/MLL1, a homologue of Drosophila TRITHORAX, modifies chromatin and is directly involved in infant acute leukaemia

Canaani, Eli; Nakamura, Tatsuya; Rozovskaia, Tanya; Smith, Sheryl T.; Mori, Toshiki; Croce, Carlo M.; Mazo, Alexander

doi:10.1038/sj.bjc.6601639

Cited by 42 publications

(35 citation statements)

References 58 publications

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“…We examined two cell lines in depth: MV4-11 and D283, both of which overexpress homeobox genes. MV4-11 is a biphenotypic leukemic cell that contains a t(4;11) translocation and resultant fusion protein that activates the mixed lineage leukemia (MLL) gene (Canaani et al, 2004). MLL is homologous to the Drosophila Trithorax chromatin modifying genes that encode proteins with histone H3K4 methyltransferase activity.…”

Section: Introductionmentioning

confidence: 99%

Differentially expressed genes are marked by histone 3 lysine 9 trimethylation in human cancer cells

Zheng

Morrison

et al. 2007

Oncogene

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Histone H3 lysine 9 trimethylation (H3K9Me3) has been associated with transcriptional repression, but recent findings implicate this chromatin modification in transcriptional activation and mRNA elongation by RNA polymerase II. Here, we applied immunoprecipitation (IP) with a custom DNA tiling microarray containing many transcription factors important in development and cancer (for example homeotic genes; N ¼ 683 total genes) to explore the relationship between H3K9Me3 and other histone modifications with the differential expression of genes. Cancer cell lines derived from different tissues (2 leukemia, 2 medulloblastoma) were characterized with IP antibodies to H3K9Me3, H3K4 dimethylation (H3K4Me2) and H3K9 acetylation (H3K9Ac). MV4-11 is known to overexpress the HOXA9 and MEIS1 genes, whereas D283 overexpresses the OTX2 homeobox gene. Gene expression was assessed by Affymetrix U133 array. Mapping the number and size of histone markings demonstrated significant colocalization of H3K9Ac and H3K4Me2 with H3K9Me3, indicating a pattern of putative 'activating' and 'repressive' markings. The median site size was 600-821 bp and 72-95% or 53-80% of chromatin signal sites were located within 1 kb or 500 bp of transcription start sites (TSS), respectively. A relatively small number of genes displayed additional H3K9Me3 sites in the 5 0 -region distant from the TSS. Comparing genes with modification sites to those without sites in their promoters confirmed the positive associations of H3K9Ac and H3K4Me2 with gene expression and revealed that H3K9Me3 is associated with active genes rather than being a repressive marking as previously thought. The positive regulatory effect of all three types of modifications were quantitatively correlated with site size, and applied to absolute gene expression within a single cell line as well as relative expression among pairs of cell lines. Extended patterns of H3K9Me3 upstream of some genes (for example HOXA9 and OTX2) may result from the action of multiple promoter elements. We found an inverse relationship between promoter DNA hypermethylation and H3K9Me3 in three studied genes (HOXA9, TMS1, RASSF1A). The localization of H3K9Me3 downstream of the TSSs of expressed genes and not within promoter regions of hypermethylated and silenced genes is consistent with the proposed coupling of H3K9Me3 with RNA polymerase II. Our results indicate a need for revising aspects of the histone code involving H3 lysine methylation. Awareness of H3K9Me3 as a mark of gene activity, not repression, is especially important for the classification of human cancer using chromatin and histone profiles.

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Section: Introductionmentioning

confidence: 99%

Differentially expressed genes are marked by histone 3 lysine 9 trimethylation in human cancer cells

Zheng

Morrison

et al. 2007

Oncogene

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“…[1][2][3][4][5][6][7][8][9][10][11][12] MLL translocations are found in at least 10% of de novo ALL and AML in children and adults. Of note, 80% of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) that arise in infants, and almost all cases of secondary AML that arise after treatment with topoisomerase II inhibitors are associated with MLL translocations.…”

Section: The Mll Leukemiamentioning

confidence: 99%

Biphasic MLL takes helm at cell cycle control: Implications in human mixed lineage leukemia

Liu¹,

Takeda²,

Cheng³

et al. 2008

Cell Cycle

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“…The H3K4 methyltransferase, mixed lineage leukemia gene1 (MLL1), which is required to maintain proper expression of homeotic HOXA and HOXC cluster genes, is frequently translocated in AML (60%) and ALL (80%) patients, and fused to about 50 different partners generating leukemogenic fusion proteins (Canaani et al, 2004;Pui et al, 1995;Martin et al, 2003;Hess, 2004). In addition, the H3K27 methyltransferase of PRC2, EZH2, is upregulated in a variety of cancers including hepatocellular, colorectal, breast, prostate, and pancreatic carcinomas (Varambally et al, 2002;Kleer et al, 2003;Matsukawa et al, 2006).…”

Section: Regulation Of Prmt Activity and Its Role In Cancermentioning

confidence: 99%

Interplay between chromatin remodelers and protein arginine methyltransferases

Pal

Sif

2007

Journal Cellular Physiology

139

124

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Chromatin modifying enzymes have emerged as key regulators of all DNA based processes, which control cell growth, development, and differentiation. Recently, it has become clear that different chromatin remodeling and histone-modifying activities are involved in transcriptional activation and repression. Among the enzymes involved in regulating chromatin structure is the family of protein arginine methyltransferases (PRMTs) that specializes in methylating both histones as well as key cellular proteins. There are eleven different PRMT genes (PRMT1-11) whose biological function remains under explored. PRMTs regulate various cellular processes such as DNA repair and transcription, RNA processing, signal transduction, and nucleo-cytoplasmic localization. Like histone lysine methylation, methylation of histone arginine residues can either induce or inhibit transcription depending on the residue being modified and the type of methylation being introduced. In this review, we will focus on the latest findings and biological roles of ATP-dependent chromatin remodeling complexes and PRMT enzymes, and how their aberrant expression is linked to cancer.

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ALL-1/MLL1, a homologue of Drosophila TRITHORAX, modifies chromatin and is directly involved in infant acute leukaemia

Cited by 42 publications

References 58 publications

Differentially expressed genes are marked by histone 3 lysine 9 trimethylation in human cancer cells

Differentially expressed genes are marked by histone 3 lysine 9 trimethylation in human cancer cells

Biphasic MLL takes helm at cell cycle control: Implications in human mixed lineage leukemia

Interplay between chromatin remodelers and protein arginine methyltransferases

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