MLL associates specifically with a subset of transcriptionally active target genes.

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 ge...

Full description

Bibliographic Details
Main Authors: Milne, T, Dou, Y, Martin, M, Brock, H, Roeder, R, Hess, J
Format: Journal article
Language:English
Published: 2005
_version_ 1826300235558682624
author Milne, T
Dou, Y
Martin, M
Brock, H
Roeder, R
Hess, J
author_facet Milne, T
Dou, Y
Martin, M
Brock, H
Roeder, R
Hess, J
author_sort Milne, T
collection OXFORD
description 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 Mll 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.
first_indexed 2024-03-07T05:14:05Z
format Journal article
id oxford-uuid:dc8ede6c-8d28-4175-8555-ebde9d08d8df
institution University of Oxford
language English
last_indexed 2024-03-07T05:14:05Z
publishDate 2005
record_format dspace
spelling oxford-uuid:dc8ede6c-8d28-4175-8555-ebde9d08d8df2022-03-27T09:18:33ZMLL associates specifically with a subset of transcriptionally active target genes.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:dc8ede6c-8d28-4175-8555-ebde9d08d8dfEnglishSymplectic Elements at Oxford2005Milne, TDou, YMartin, MBrock, HRoeder, RHess, JMLL (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 Mll 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.
spellingShingle Milne, T
Dou, Y
Martin, M
Brock, H
Roeder, R
Hess, J
MLL associates specifically with a subset of transcriptionally active target genes.
title MLL associates specifically with a subset of transcriptionally active target genes.
title_full MLL associates specifically with a subset of transcriptionally active target genes.
title_fullStr MLL associates specifically with a subset of transcriptionally active target genes.
title_full_unstemmed MLL associates specifically with a subset of transcriptionally active target genes.
title_short MLL associates specifically with a subset of transcriptionally active target genes.
title_sort mll associates specifically with a subset of transcriptionally active target genes
work_keys_str_mv AT milnet mllassociatesspecificallywithasubsetoftranscriptionallyactivetargetgenes
AT douy mllassociatesspecificallywithasubsetoftranscriptionallyactivetargetgenes
AT martinm mllassociatesspecificallywithasubsetoftranscriptionallyactivetargetgenes
AT brockh mllassociatesspecificallywithasubsetoftranscriptionallyactivetargetgenes
AT roederr mllassociatesspecificallywithasubsetoftranscriptionallyactivetargetgenes
AT hessj mllassociatesspecificallywithasubsetoftranscriptionallyactivetargetgenes