MLL associates specifically with a subset of transcriptionally active target genes

Thomas A. Milne, Yali Dou, Mary Ellen Martin, Hugh W. Brock, Robert G. Roeder, Jay Hess

Research output: Contribution to journalArticle

149 Citations (Scopus)

Abstract

MLL (mixed-lineage leukemia) is a histone H3 Lys-4 specific methyltransferase that is a positive regulator of Hox expression. MLL rearrangements and amplification are common in acute lymphoid and myeloid leukemias and myelodysplastic disorders and are associated with abnormal up-regulation of Hox gene expression. Although MLL is expressed throughout hematopoiesis, Hox gene expression is sharply down-regulated during differentiation, suggesting that either the activity of MLL or its association with target promoters must be regulated. Here we show that MLL associates with actively transcribed genes but does not remain bound after transcriptional down-regulation. Surprisingly, MLL is associated not only with promoter regions but also is distributed across the entire coding regions of genes. MLL interacts with RNA polymerase II (pol II) and colocalizes with RNA pol II at a subset of actively transcribed target in vivo. Loss of function MII results in defects in RNA pol II distribution. Together the results suggest that an intimate association between MLL and RNA pol II occurs at MLL target genes in vivo that is required for normal initiation and/or transcriptional elongation.

Original languageEnglish (US)
Pages (from-to)14765-14770
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number41
DOIs
StatePublished - Oct 11 2005
Externally publishedYes

Fingerprint

Leukemia
RNA Polymerase II
Genes
Homeobox Genes
Hematopoiesis
Methyltransferases
Gene Expression Regulation
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Genetic Promoter Regions
Acute Myeloid Leukemia
Histones
Up-Regulation
Down-Regulation
Gene Expression

Keywords

  • Histone methyltransferase
  • Hox genes
  • Transcription

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

MLL associates specifically with a subset of transcriptionally active target genes. / Milne, Thomas A.; Dou, Yali; Martin, Mary Ellen; Brock, Hugh W.; Roeder, Robert G.; Hess, Jay.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 102, No. 41, 11.10.2005, p. 14765-14770.

Research output: Contribution to journalArticle

Milne, Thomas A. ; Dou, Yali ; Martin, Mary Ellen ; Brock, Hugh W. ; Roeder, Robert G. ; Hess, Jay. / MLL associates specifically with a subset of transcriptionally active target genes. In: Proceedings of the National Academy of Sciences of the United States of America. 2005 ; Vol. 102, No. 41. pp. 14765-14770.
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