MOZ-TIF2-induced acute myeloid leukemia requires the MOZ nucleosome binding motif and TIF2-mediated recruitment of CBP

Deguchi, Kenji; Ayton, Paul M.; Carapeti, Melina; Kutok, Jeffery L.; Snyder, Cynthia S.; Williams, Ifor R.; Cross, Nicholas C. P.; Glass, Christopher K.; Cleary, Michael L.; Gilliland, D. Gary

doi:10.1016/s1535-6108(03)00051-5

Cited by 198 publications

(191 citation statements)

References 48 publications

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“…The CBP/p300-interacting domain (CID) of TIF2 remains intact in MOZ-TIF2 resulting from inv(8)(p11;q13), suggesting that this fusion protein acts through p300 and CBP and that aberrant acetylation plays a role in leukemogenesis (Figure 3b). MOZ-TIF2 displays intrinsic transforming ability in vitro and induces AML in murine bone marrow transplant assays (Deguchi et al, 2003). In support of the involvement of p300 and CBP, the CID of TIF2 is crucial for these activities.…”

Section: Moz and Morf In Leukemia Leiomyomata And Other Malignanciesmentioning

confidence: 95%

MOZ and MORF, two large MYSTic HATs in normal and cancer stem cells

2007

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Genes of the human monocytic leukemia zinc-finger protein MOZ (HUGO symbol, MYST3) and its paralog MORF (MYST4) are rearranged in chromosome translocations associated with acute myeloid leukemia and/or benign uterine leiomyomata. Both proteins have intrinsic histone acetyltransferase activity and are components of quartet complexes with noncatalytic subunits containing the bromodomain, plant homeodomain-linked (PHD) finger and proline-tryptophan-tryptophan-proline (PWWP)-containing domain, three types of structural modules characteristic of chromatin regulators. Although leukemia-derived fusion proteins such as MOZ-TIF2 promote self-renewal of leukemic stem cells, recent studies indicate that murine MOZ and MORF are important for proper development of hematopoietic and neurogenic progenitors, respectively, thereby highlighting the importance of epigenetic integrity in safeguarding stem cell identity.

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Section: Moz and Morf In Leukemia Leiomyomata And Other Malignanciesmentioning

confidence: 95%

MOZ and MORF, two large MYSTic HATs in normal and cancer stem cells

2007

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“…Thus, the fusion protein induces properties typical of leukaemic stem cells. Interestingly, the intrinsic HAT activity of MOZ is required for neither self-renewal nor leukaemic transformation, but its nucleosome-binding motif is essential for both [103,104]. Importantly, the CBP interaction domain within TIF2 is also essential for both processes [103,104].…”

Section: Histone Modifications and Cancermentioning

confidence: 99%

Regulation of chromatin by histone modifications

2011

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Chromatin is not an inert structure, but rather an instructive DNA scaffold that can respond to external cues to regulate the many uses of DNA. A principle component of chromatin that plays a key role in this regulation is the modification of histones. There is an ever-growing list of these modifications and the complexity of their action is only just beginning to be understood. However, it is clear that histone modifications play fundamental roles in most biological processes that are involved in the manipulation and expression of DNA. Here, we describe the known histone modifications, define where they are found genomically and discuss some of their functional consequences, concentrating mostly on transcription where the majority of characterisation has taken place.

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“…Recent biochemical purifications revealed that both the Drosophila and mammalian MOF proteins reside in multi-protein complexes and that most of these interacting proteins are conserved between Drosophila and mammals (Table 2; Dou et al, 2005;Smith et al, 2005;Mendjan et al, 2006). Co-purification of four human MSL proteins (hMSL1, hMSL2, hMSL3 and hMOF) showed that the MSL (Borrow et al, 1996;Carapeti et al, 1998;Champagne et al, 1999Champagne et al, , 2001Chaffanet et al, 2000;Kitabayashi et al, 2001;Pelletier et al, 2002;Bristow and Shore, 2003;Deguchi et al, 2003;Kindle et al, 2005;Katsumoto et al, 2006;Thomas et al, 2006;Ohta et al, 2007 Abbreviation: HAT, histone acetyltransferases.…”

Section: The Histone Acetyltransferase Mofmentioning

confidence: 99%

Males absent on the first (MOF): from flies to humans

2007

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Histone modifications such as acetylation, methylation and phosphorylation have been implicated in fundamental cellular processes such as epigenetic regulation of gene expression, organization of chromatin structure, chromosome segregation, DNA replication and DNA repair. Males absent on the first (MOF) is responsible for acetylating histone H4 at lysine 16 (H4K16) and is a key component of the MSL complex required for dosage compensation in Drosophila. The human ortholog of MOF (hMOF) has the same substrate specificity and recent purification of the human and Drosophila MOF complexes showed that these complexes were also highly conserved through evolution. Several studies have shown that loss of hMOF in mammalian cells leads to a number of different phenotypes; a G 2 /M cell cycle arrest, nuclear morphological defects, spontaneous chromosomal aberrations, reduced transcription of certain genes and an impaired DNA repair response upon ionizing irradiation. Moreover, hMOF is involved in ATM activation in response to DNA damage and acetylation of p53 by hMOF influences the cell's decision to undergo apoptosis instead of a cell cycle arrest. These data, highlighting hMOF as an important component of many cellular processes, as well as links between hMOF and cancer will be discussed.

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MOZ-TIF2-induced acute myeloid leukemia requires the MOZ nucleosome binding motif and TIF2-mediated recruitment of CBP

Cited by 198 publications

References 48 publications

MOZ and MORF, two large MYSTic HATs in normal and cancer stem cells

MOZ and MORF, two large MYSTic HATs in normal and cancer stem cells

Regulation of chromatin by histone modifications

Males absent on the first (MOF): from flies to humans

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