Abstract
Proteins encoded by Polycomb and Trithorax-group (Pc-G and Trx-G) genes regulate developmental fates by maintaining or repressing HOX gene expression, respectively. In a search for candidate myeloid leukemia tumor suppressor genes from a ∼2.5 Mb commonly-deleted segment within chromosome band 7q22, we identified a novel human Trithorax (Trx) family member named MLL5. Trx-G genes encode proteins that modulate transcriptional programs through protein–protein interactions that are mediated by PHD and SET domains, and by binding to DNA via A-T hooks and methyltransferase homology motifs. MLL5 is a homolog of the Drosophila gene CG9007; it encodes a 6.5 kb mRNA that is expressed widely. MLL5 includes a SET domain and a single PHD finger, but lacks A-T hooks and methyltransferase homology domains that are found in MLL. The leukemia cell line RCV-ACV-A carries a heterozygous missense mutation within the PHD domain; however, no mutations within the MLL5 coding region were detected in primary leukemias. MLL5 is a novel mammalian Trx-G gene that might modulate transcription by protein association.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Alkema MJ, Jacobs H, van Lohuizen M, Berns A . 1997 Oncogene 15: 899–910
Allen RJ, Smith SD, Moldwin RL, Lu MM, Giordano L, Vignon C, Suto Y, Harden A, Tomek R, Veldman T, Ried T, Larson RA, Le Beau MM, Rowley JD, Zeleznik-Le N . 1998 Leukemia 12: 1119–1127
Baylin SB, Belinsky SA, Herman JG . 2000 J. Natl. Cancer Inst. 92: 1460–1461
Borrow J, Shearman AM, Stanton Jr VP, Becher R, Collins T, Williams AJ, Dube I, Katz F, Kwong YL, Morris C, Ohyashiki K, Toyama K, Rowley J, Housman DE . 1996 Nat. Genet. 12: 159–167
Canaani E, Nowell PC, Croce CM . 1995 Adv. Cancer Res. 66: 213–234
Corral J, Lavenir I, Impey H, Warren AJ, Forster A, Larson TA, Bell S, McKenzie AN, King G, Rabbitts TH . 1996 Cell 85: 853–861
Dimartino JF, Cleary ML . 1999 Br. J. Haematol. 106: 614–626
Dobson CL, Warren AJ, Pannell R, Forster A, Lavenir I, Corral J, Smith AJ, Rabbitts TH . 1999 EMBO J. 18: 3564–3574
Gould A . 1997 Curr. Opin. Genet. Dev. 7: 488–494
Hanahan D, Weinberg RA . 2000 Cell 100: 57–70
Hanson RD, Hess JL, Yu BD, Ernst P, van Lohuizen M, Berns A, van der Lugt NM, Shashikant CS, Ruddle FH, Seto M, Korsmeyer SJ . 1999 Proc. Natl. Acad. Sci. USA 96: 14372–14377
Kalra R, Paderanga D, Olson K, Shannon KM . 1994 Blood 84: 3435–3439
Kaneko Y, Maseki N, Sakuri M, Shibuya A, Shinohara T, Fujimoto T, Kanno H, Nishikawa A . 1989 Leukemia 3: 36–41
Kratz CP, Emerling BM, Donovan S, Laig-Webster M, Taylor BR, Thompson P, Jensen S, Banerjee A, Bonifas J, Makalowski W, Green ED, Le Beau MM, Shannon KM . 2001 Genomics 77: 171–180
Lavau C, Du C, Thirman M, Zeleznik-Le N . 2000 EMBO J. 19: 4655–4664
Lawrence HJ, Largman C . 1992 Blood 80: 2445–2453
Le Beau M, Albain KS, Larson RA, Vardiman J, Davis E, Blough R, Golomb H, Rowley J . 1986 J. Clin. Oncol. 3: 325–345
Le Beau MM, Espinosa III R, Davis EM, Eisenbart JD, Larson RA, Green ED . 1996 Blood 88: 1930–1935
Lessard J, Baban S, Sauvageau G . 1998 Blood 91: 1216–1224
Look A . 1997 Science 278: 1059–1064
Luna-Fineman S, Shannon K, Lange BJ . 1995 Blood 85: 1985–1999
Luna-Fineman S, Shannon KM, Atwater SK, Davis J, Masterson M, Ortega J, Sanders J, Steinherz P, Weinberg V, Lange BJ . 1999 Blood 93: 459–466
Nakamura T, Largaespada DA, Lee MP, Johnson LA, Ohyashiki K, Toyama K, Chen SJ, Willman CL, Chen IM, Feinberg AP, Jenkins NA, Copeland NG, Shaughnessy Jr JD . 1996a Nat. Genet. 12: 154–158
Nakamura T, Largaespada DA, Shaughnessy Jr JD, Jenkins NA, Copeland NG . 1996b Nat. Genet. 12: 149–153
Rowley JD . 1999 Semin. Hematol. 36: 59–72
Rozovskaia T, Rozenblatt-Rosen O, Sedkov Y, Burakov D, Yano T, Nakamura T, Petruck S, Ben-Simchon L, Croce CM, Mazo A, Canaani E . 2000 Oncogene 19: 351–357
Rozovskaia T, Tillib S, Smith S, Sedkov Y, Rozenblatt-Rosen O, Petruk S, Yano T, Nakamura T, Ben-Simchon L, Gildea J, Croce CM, Shearn A, Canaani E, Mazo A . 1999 Mol. Cell. Biol. 19: 6441–6447
Side L, Taylor B, Cayouette M, Connor E, Thompson P, Luce M, Shannon K . 1997 N. Engl. J. Med. 336: 1713–1720
Slany RK, Lavau C, Cleary ML . 1998 Mol. Cell. Biol. 18: 122–129
Song WJ, Sullivan MG, Legare RD, Hutchings S, Tan X, Kufrin D, Ratajczak J, Resende IC, Haworth C, Hock R, Loh M, Felix C, Roy DC, Busque L, Kurnit D, Willman C, Gewirtz AM, Speck NA, Bushweller JH, Li FP, Gardiner K, Poncz M, Maris JM, Gilliland DG . 1999 Nat. Genet. 23: 166–175
Thirman MJ, Larson RA . 1996 Hematol. Oncol. Clin. North Am. 10: 293–320
van Lohuizen M . 1999 Curr. Opin. Genet. Dev. 9: 355–361
Yagi H, Deguchi K, Aono A, Tani Y, Kishimoto T, Komori T . 1998 Blood 92: 108–117
Yu B, Hess JL, Horning SE, Brown GAJ, Korsmeyer S . 1995 Nature 378: 505–508
Zeleznik-Le NJ, Harden AM, Rowley JD . 1994 Proc. Natl. Acad. Sci. USA 91: 10610–10614
Acknowledgements
This work was supported by PHS grant CA40046 (to MM Le Beau and KM Shannon), by the Frank A Campini Foundation (to KM Shannon), and by a fellowship grant from the Dr Mildred Scheel Stiftung für Krebsforschung (to CP Kratz). These studies were also facilitated by a collaboration with the Children's Oncology Group (Study Number B24), and by the gift of an ABI 7700 Sequence Detection System from Applied Biosystems.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Emerling, B., Bonifas, J., Kratz, C. et al. MLL5, a homolog of Drosophila trithorax located within a segment of chromosome band 7q22 implicated in myeloid leukemia. Oncogene 21, 4849–4854 (2002). https://doi.org/10.1038/sj.onc.1205615
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1205615
Keywords
This article is cited by
-
Epigenetic genes and epilepsy — emerging mechanisms and clinical applications
Nature Reviews Neurology (2022)
-
MLL5 improves ATRA driven differentiation and promotes xenotransplant engraftment in acute promyelocytic leukemia model
Cell Death & Disease (2021)
-
Why are so many MLL lysine methyltransferases required for normal mammalian development?
Cellular and Molecular Life Sciences (2019)
-
MLL5 (KMT2E): structure, function, and clinical relevance
Cellular and Molecular Life Sciences (2017)
-
−7/7q− syndrome in myeloid-lineage hematopoietic malignancies: attempts to understand this complex disease entity
Oncogene (2015)