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Oncogene (2007) 26, 54085419 & 2007 Nature Publishing Group All rights reserved 0950-9232/07 $30.00 www.nature.com/onc
REVIEW
MOZ and MORF, two large MYSTic HATs in normal and cancer stem cells
X-J Yang and M Ullah
Molecular Oncology Group, Department of Medicine, McGill University Health Center, Montral, Qubec, Canada
Genes of the human monocytic leukemia zinc-nger 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 withnoncatalytic subunits containing the bromo-domain, plant homeodomain-linked (PHD) nger 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.
Oncogene (2007) 26, 54085419; doi:10.1038/sj.onc.1210609
Keywords: lysine acetylation; MYST acetyltransferase; ING5; BR140; CBP; Runx1
Introduction
Like many other human diseases, cancer is a pathological condition with genetic and epigenetic basis (reviewed in Baylin and Herman, 2000; Jaenisch and Bird, 2003; Egger et al., 2004). Although genetic alteration is irreversible, epigenetic changes are sometimes reversible. Diet, lifestyle, social interaction and environmental cues can trigger the reset of epigenetic programs, opening unique windows of opportunity for potential therapeutic intervention (for reviews, see Egger et al., 2004; Wade and Archer, 2006; Nuyt and Szyf, 2007). How nuclear DNA is packaged into chromatin is a major epigenetic determinant. The specic chromatin organization in a given cell type (that is, the packaging state of nuclear DNA) is important for its unique gene expression pattern. A cancer cell may possess an aberrant chromatin organization and thus an abnormal gene expression
pattern. For cancer biology, it is thus important to understand the fundamental mechanisms whereby chromatin structure and function are regulated. In the past two decades, our knowledge about regulation in this eld has exploded. Known regulatory mechanisms include chromatin assembly, ATP-dependent remodeling, covalent modication, condensin-mediated condensation, replacement with histone variants, and association of noncoding RNA (reviewed by Horn and Peterson, 2002; Khorasanizadeh, 2004; Li et al., 2007). Covalent modication can occur at both...