Crosstalk Between Epigenetic Readers Regulates the MOZ/MORF HAT Complexes

Overview

Journal Epigenetics

Specialty Genetics

Date 2013 Oct 31

PMID 24169304

Citations 42

Authors

Brianna J Klein

Marie-Eve Lalonde

Jacques Cote

Xiang-Jiao Yang

Tatiana G Kutateladze

Affiliations

Soon will be listed here.

Abstract

The MOZ/MORF complexes represent an example of a chromatin-binding assembly whose recruitment to specific genomic regions and activity can be fine-tuned by posttranslational modifications of histones. Here we detail the structures and biological functions of epigenetic readers present in the four core subunits of the MOZ/MORF complexes, highlight the imperative role of combinatorial readout by the multiple readers, and discuss new research directions to advance our understanding of histone acetylation.

Citing Articles

Epigene functional diversity: isoform usage, disordered domain content, and variable binding partners.

Bondhus L, Nava A, Liu I, Arboleda V Epigenetics Chromatin. 2025; 18(1):8.

PMID: 39893491 PMC: 11786378. DOI: 10.1186/s13072-025-00571-z.

A multivalent engagement of ENL with MOZ.

Becht D, Selvam K, Lachance C, Cote V, Li K, Nguyen M Nat Struct Mol Biol. 2025; .

PMID: 39794553 DOI: 10.1038/s41594-024-01455-8.

The small inhibitor WM-1119 effectively targets KAT6A-rearranged AML, but not KMT2A-rearranged AML, despite shared KAT6 genetic dependency.

Sheridan M, Maqbool M, Largeot A, Clayfield L, Xu J, Moncaut N J Hematol Oncol. 2024; 17(1):91.

PMID: 39380002 PMC: 11462755. DOI: 10.1186/s13045-024-01610-0.

A MOZ-TIF2 leukemia mouse model displays KAT6-dependent H3K23 propionylation and overexpression of a set of active developmental genes.

Smolko A, Sullivan D, Olsen S, Kang H, Whedon S, Baell J Proc Natl Acad Sci U S A. 2024; 121(26):e2405905121.

PMID: 38889153 PMC: 11214132. DOI: 10.1073/pnas.2405905121.

HBO1, a MYSTerious KAT and its links to cancer.

Yokoyama A, Niida H, Kutateladze T, Cote J Biochim Biophys Acta Gene Regul Mech. 2024; 1867(3):195045.

PMID: 38851533 PMC: 11330361. DOI: 10.1016/j.bbagrm.2024.195045.

References

Ali M, Yan K, Lalonde M, Degerny C, Rothbart S, Strahl B . Tandem PHD fingers of MORF/MOZ acetyltransferases display selectivity for acetylated histone H3 and are required for the association with chromatin. J Mol Biol. 2012; 424(5):328-38. PMC: 3502708. DOI: 10.1016/j.jmb.2012.10.004. View

Miller C, Maves L, Kimmel C . moz regulates Hox expression and pharyngeal segmental identity in zebrafish. Development. 2004; 131(10):2443-61. DOI: 10.1242/dev.01134. View

Yang X . The diverse superfamily of lysine acetyltransferases and their roles in leukemia and other diseases. Nucleic Acids Res. 2004; 32(3):959-76. PMC: 384351. DOI: 10.1093/nar/gkh252. View

Qiu Y, Liu L, Zhao C, Han C, Li F, Zhang J . Combinatorial readout of unmodified H3R2 and acetylated H3K14 by the tandem PHD finger of MOZ reveals a regulatory mechanism for HOXA9 transcription. Genes Dev. 2012; 26(12):1376-91. PMC: 3387664. DOI: 10.1101/gad.188359.112. View

Voss A, Vanyai H, Collin C, Dixon M, McLennan T, Sheikh B . MOZ regulates the Tbx1 locus, and Moz mutation partially phenocopies DiGeorge syndrome. Dev Cell. 2012; 23(3):652-63. PMC: 3442180. DOI: 10.1016/j.devcel.2012.07.010. View

Huntly B, Shigematsu H, Deguchi K, Lee B, Mizuno S, Duclos N . MOZ-TIF2, but not BCR-ABL, confers properties of leukemic stem cells to committed murine hematopoietic progenitors. Cancer Cell. 2004; 6(6):587-96. DOI: 10.1016/j.ccr.2004.10.015. View

Kutateladze T . Translation of the phosphoinositide code by PI effectors. Nat Chem Biol. 2010; 6(7):507-13. PMC: 3182472. DOI: 10.1038/nchembio.390. View

Falk H, Connor T, Yang H, Loft K, Alcindor J, Nikolakopoulos G . An efficient high-throughput screening method for MYST family acetyltransferases, a new class of epigenetic drug targets. J Biomol Screen. 2011; 16(10):1196-205. DOI: 10.1177/1087057111421631. View

Yang X, Ullah M . MOZ and MORF, two large MYSTic HATs in normal and cancer stem cells. Oncogene. 2007; 26(37):5408-19. DOI: 10.1038/sj.onc.1210609. View

10.

Chaffanet M, Gressin L, Preudhomme C, Soenen-Cornu V, Birnbaum D, Pebusque M . MOZ is fused to p300 in an acute monocytic leukemia with t(8;22). Genes Chromosomes Cancer. 2000; 28(2):138-44. DOI: 10.1002/(sici)1098-2264(200006)28:2<138::aid-gcc2>3.0.co;2-2. View

11.

Borrow J, Stanton Jr V, Andresen J, Becher R, Behm F, Chaganti R . The translocation t(8;16)(p11;p13) of acute myeloid leukaemia fuses a putative acetyltransferase to the CREB-binding protein. Nat Genet. 1996; 14(1):33-41. DOI: 10.1038/ng0996-33. View

12.

Champagne N, Pelletier N, Yang X . The monocytic leukemia zinc finger protein MOZ is a histone acetyltransferase. Oncogene. 2001; 20(3):404-9. DOI: 10.1038/sj.onc.1204114. View

13.

Qin S, Jin L, Zhang J, Liu L, Ji P, Wu M . Recognition of unmodified histone H3 by the first PHD finger of bromodomain-PHD finger protein 2 provides insights into the regulation of histone acetyltransferases monocytic leukemic zinc-finger protein (MOZ) and MOZ-related factor (MORF). J Biol Chem. 2011; 286(42):36944-55. PMC: 3196140. DOI: 10.1074/jbc.M111.244400. View

14.

Lalonde M, Avvakumov N, Glass K, Joncas F, Saksouk N, Holliday M . Exchange of associated factors directs a switch in HBO1 acetyltransferase histone tail specificity. Genes Dev. 2013; 27(18):2009-24. PMC: 3792477. DOI: 10.1101/gad.223396.113. View

15.

Cengiz B, Gunduz E, Gunduz M, Beder L, Tamamura R, Bagci C . Tumor-specific mutation and downregulation of ING5 detected in oral squamous cell carcinoma. Int J Cancer. 2010; 127(9):2088-94. DOI: 10.1002/ijc.25224. View

16.

Christensen J, Elfving B, Muller H, Fryland T, Nyegaard M, Corydon T . The Schizophrenia and Bipolar Disorder associated BRD1 gene is regulated upon chronic restraint stress. Eur Neuropsychopharmacol. 2012; 22(9):651-6. DOI: 10.1016/j.euroneuro.2012.01.005. View

17.

Nebral K, Denk D, Attarbaschi A, Konig M, Mann G, Haas O . Incidence and diversity of PAX5 fusion genes in childhood acute lymphoblastic leukemia. Leukemia. 2008; 23(1):134-43. DOI: 10.1038/leu.2008.306. View

18.

Szakszon K, Salpietro C, Kakar N, Knegt A, Olah E, Dallapiccola B . De novo mutations of the gene encoding the histone acetyltransferase KAT6B in two patients with Say-Barber/Biesecker/Young-Simpson syndrome. Am J Med Genet A. 2013; 161A(4):884-8. DOI: 10.1002/ajmg.a.35848. View

19.

Soliman M, Riabowol K . After a decade of study-ING, a PHD for a versatile family of proteins. Trends Biochem Sci. 2007; 32(11):509-19. DOI: 10.1016/j.tibs.2007.08.006. View

20.

Pelletier N, Champagne N, Stifani S, Yang X . MOZ and MORF histone acetyltransferases interact with the Runt-domain transcription factor Runx2. Oncogene. 2002; 21(17):2729-40. DOI: 10.1038/sj.onc.1205367. View