A COMPASS in the voyage of defining the role of trithorax/MLL-containing complexes: Linking leukemogensis to covalent modifications of chromatin

Tenney, Kristen; Shilatifard, Ali

doi:10.1002/jcb.20421

Cited by 75 publications

(89 citation statements)

References 47 publications

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“…This histone H3 modification in mammals is required for proper regulation of HOX gene expression. [26][27][28] The compositional and functional conservation between MLL and Set1 complexes establishes the existence of highly conserved, ancient molecular machinery for histone H3 methylation on K4 and emphasizes applicability of the yeast findings to the mammalian system.…”

Section: Regulation Of Histone Modifications By Bur1/bur2 Complexmentioning

confidence: 98%

Bur1/Bur2 and the Ctk Complex in Yeast: The Split Personality of Mammalian P-TEFb

Wood

Shilatifard

2006

Cell Cycle

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Eukaryotic organisms possess a host of factors that regulate transcriptional elongation. In higher eukaryotes, the transcription factor P-TEFb not only regulates phosphorylation of the RNA polymerase II C-terminal domain, but it also inhibits the action of transcriptional repressors and is required for the association of several elongation factors with the transcribing polymerase. In the yeast Saccharomyces cerevisiae, the cyclin dependent kinases Bur1/Bur2 and Ctk complex (Ctk1, 2 and 3) are also able to impact several aspects of transcription. Together, these two kinase complexes appear to functionally reconstitute the activity of P-TEFb in yeast. Recent findings regarding the role of these kinases in histone tail modifications and transcriptional regulation is briefly reviewed below.

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Section: Regulation Of Histone Modifications By Bur1/bur2 Complexmentioning

confidence: 98%

Bur1/Bur2 and the Ctk Complex in Yeast: The Split Personality of Mammalian P-TEFb

Wood

Shilatifard

2006

Cell Cycle

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“…The mechanistic basis for the initiation of these leukemias has not been definitively elucidated, but it appears to be related to the function of the protein product of the MLL gene. MLL, which is the human homolog of the Drosophila trithorax and yeast Set1 proteins, is a histone methyltransferase that is involved in transcriptional regulation in hematopoietic cells [94][95][96][97][98]. Accumulating evidence suggests that the fusion of the MLL protein with other cellular partner proteins alters enzyme function and affects the differentiation of pluripotent hematopoietic stem cells or committed myeloid or lymphoid stem cells by deregulating the expression of the HOX gene [94][95][96]98,99].…”

Section: Topoisomerase II As a Genotoxic Enzymementioning

confidence: 99%

DNA topoisomerase II, genotoxicity, and cancer

McClendon

Osheroff

2007

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

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466

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Type II topoisomerases are ubiquitous enzymes that play essential roles in a number of fundamental DNA processes. They regulate DNA under-and overwinding, and resolve knots and tangles in the genetic material by passing an intact double helix through a transient double-stranded break that they generate in a separate segment of DNA. Because type II topoisomerases generate DNA strand breaks as a requisite intermediate in their catalytic cycle, they have the potential to fragment the genome every time they function. Thus, while these enzymes are essential to the survival of proliferating cells, they also have significant genotoxic effects. This latter aspect of type II topoisomerase has been exploited for the development of several classes of anticancer drugs that are widely employed for the clinical treatment of human malignancies. However, considerable evidence indicates that these enzymes also trigger specific leukemic chromosomal translocations. In light of the impact, both positive and negative, of type II topoisomerases on human cells, it is important to understand how these enzymes function and how their actions can destablize the genome. This article discusses both aspects of human type II topoisomerases.

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“…Set1/KMT2 alone is not enzymatically active, but functions within COMPASS and is capable of mono-, di-, and trimethylating H3K4 [6,8,10,[24][25][26][27]. Following the identification of Set1/COMPASS as an H3K4 methylase, it was demonstrated that its mammalian homologues, the MLL proteins, MLL1-4 and hSet1A and B, are found in COMPASS-like complexes capable of methylating the fourth lysine of histone H3 [6,28,29] (Figure 2). While there is only one Set1 in yeast, there are over six Set1 related proteins in mammals, all capable of catalyzing the methylation of H3K4 (Figure 2).…”

Section: Enzymatic Machinery Required For H3k4 Methylationmentioning

confidence: 99%

Molecular implementation and physiological roles for histone H3 lysine 4 (H3K4) methylation

Shilatifard

2008

Current Opinion in Cell Biology

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Chromosomal surfaces are ornamented with a variety of posttranslational modifications of histones, which are required for the regulation of many of the DNA-templated processes. Such histone modifications include acetylation, sumoylation, phosphorylation, ubiquitination and methylation. Histone modifications can either function by disrupting chromosomal contacts or by regulating nonhistone protein interactions with chromatin. In this review, recent findings will be discussed regarding the regulation of the implementation and physiological significance for one such histone modification, histone H3 Lysine 4 (H3K4) methylation by the yeast COMPASS and mammalian COMPASS-like complexes.All DNA-templated processes are regulated by chromatin and its posttranslational modifications. The nucleosome, which is the fundamental unit of chromatin, is composed of 146 base pairs of DNA wrapped twice around an octamer of the four core histones (H3, H4, H2A, and H2B) [1][2][3]. Structural studies demonstrated that the unstructured histone N-terminal tails protrude outward from the nucleosomes and are available for interactions with other neighboring histones or non-histone proteins. Many residues within the histone N-terminal tails and a few within the histone core can be altered by posttranslational modifications [1]. To date, there are at least five types of posttranslational modifications found on histones, these include: acetylation, phosphorylation, ubiquitination, sumoylation, and methylation [4,5]. Almost all of these modifications have been shown to be reversible, and their implementation and removal are fundamental to the regulation of a diverse set of biological processes such as replication, repair, recombination, transcription and RNA processing [4,5]. This review will focus mainly on the most recent studies of one type of histone modification, histone H3 lysine 4 (H3K4) methylation. Histone lysine methylationHistones are methylated either on their arginine and/or lysine residues [6,7]. The lysine residues are methylated on the ε-nitrogen by either the SET domain or the non-SET domain-containing lysine methyltransferases (KMTs). A large number of enzymes have been characterized which are capable of methylating specific lysine residues on histones ( Table 1). The ε-nitrogen can also be modified by lysine acetyl transferases (KATs) and methylation and acetylation of lysine are mutually exclusive. Indeed, many sites of histone methylation are also sites of acetylation.Correspondence and proofs should be sent to the following address: Ali Shilatifard, Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, Office (816) 926-4465, Email: ASH@Stowers-Institute.org. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable for...

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A COMPASS in the voyage of defining the role of trithorax/MLL-containing complexes: Linking leukemogensis to covalent modifications of chromatin

Cited by 75 publications

References 47 publications

Bur1/Bur2 and the Ctk Complex in Yeast: The Split Personality of Mammalian P-TEFb

Bur1/Bur2 and the Ctk Complex in Yeast: The Split Personality of Mammalian P-TEFb

DNA topoisomerase II, genotoxicity, and cancer

Molecular implementation and physiological roles for histone H3 lysine 4 (H3K4) methylation

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