hDOT1L links histone methylation to leukemogenesis.

hDOT1L links histone methylation to leukemogenesis. Research Abstract Details 

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hDOT1L links histone methylation to leukemogenesis. Abstract Text:

Yuki Okada,Qin Feng,Yihui Lin,Qi Jiang,Yaqiang Li,Vernon M Coffield,Lishan Su,Guoliang Xu,Yi Zhang,

Epigenetic modifications play an important role in human cancer. One such modification, histone methylation, contributes to human cancer through deregulation of cancer-relevant genes. The yeast Dot1 and its human counterpart, hDOT1L, methylate lysine 79 located within the globular domain of histone H3. Here we report that hDOT1L interacts with AF10, an MLL (mixed lineage leukemia) fusion partner involved in acute myeloid leukemia, through the OM-LZ region of AF10 required for MLL-AF10-mediated leukemogenesis. We demonstrate that direct fusion of hDOT1L to MLL results in leukemic transformation in an hDOT1L methyltransferase activity-dependent manner. Transformation by MLL-hDOT1L and MLL-AF10 results in upregulation of a number of leukemia-relevant genes, such as Hoxa9, concomitant with hypermethylation of H3-K79. Our studies thus establish that mistargeting of hDOT1L to Hoxa9 plays an important role in MLL-AF10-mediated leukemogenesis and suggests that the enzymatic activity of hDOT1L may provide a potential target for therapeutic intervention.

hDOT1L links histone methylation to leukemogenesis. Publishing Authors By Initials

Y Okada,Q Feng,Y Lin,Q Jiang,Y Li,VM Coffield,L Su,G Xu,Y Zhang,

For similar genetic processes: gene expression regulation: up-regulation research abstracts see: genetic processes: gene expression regulation: up-regulation research

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MEDLINE DATE:

hDOT1L links histone methylation to leukemogenesis. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Cell

VOLUME: 121

Page Numbers: 167-78

Journal Abbreviation: Cell

ISSN: 0092-8674

DAY: 22

MONTH: Apr

YEAR: 2005

hDOT1L links histone methylation to leukemogenesis. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 413066

hDOT1L links histone methylation to leukemogenesis. Keywords Mesh Terms:

KEYWORDS: Up-Regulation

MESH TERMS: metabolism

Chemical & Substance for Abstract: hDOT1L links histone methylation to leukemogenesis. Information

Substance Name: Methyltransferases

Registry Number: EC 2.1.1.-

Grant and Affiliation Information for hDOT1L links histone methylation to leukemogenesis.

AFFILIATION: Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.

Country: United States

AGENCY: United States NCI

GRANT: R01 CA119133-01A1

ACRONYM: CA

MEDLINETA: Cell

REFSOURCE: Cell. 2005 Jun 3;121(5):809

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ACCESSION NUMBER:

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