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BCL11B functionally associates with the NuRD complex in T lymphocytes to repress targeted promoter

Cismasiu, Valeriu LU ; Adamo, Karen ; Gecewicz, Jennifer ; Duque, Javier ; Lin, Qishan and Avram, Dorina (2005) In Oncogene 24(45). p.6753-6764
Abstract
BCL11 genes play crucial roles in lymphopoiesis and have been associated with hematopoietic malignancies. Specifically, disruption of the BCL11B (B-cell chronic lymphocytic leukemia/lymphoma 11B) locus is linked to T-cell acute lymphoblastic leukemia, and the loss of heterozygosity in mice results in T-cell lymphoma. BCL11 proteins are related C2H2 zinc-finger transcription factors that act as transcriptional repressors. Here, we demonstrate the association of the endogenous BCL11B with the nucleosome remodeling and histone deacetylase (NuRD) complex, one of the major transcriptional corepressor complexes in mammalian cells. BCL11B complexes from T lymphocytes possess trichostatin A-sensitive histone deacetylase activity, confirming the... (More)
BCL11 genes play crucial roles in lymphopoiesis and have been associated with hematopoietic malignancies. Specifically, disruption of the BCL11B (B-cell chronic lymphocytic leukemia/lymphoma 11B) locus is linked to T-cell acute lymphoblastic leukemia, and the loss of heterozygosity in mice results in T-cell lymphoma. BCL11 proteins are related C2H2 zinc-finger transcription factors that act as transcriptional repressors. Here, we demonstrate the association of the endogenous BCL11B with the nucleosome remodeling and histone deacetylase (NuRD) complex, one of the major transcriptional corepressor complexes in mammalian cells. BCL11B complexes from T lymphocytes possess trichostatin A-sensitive histone deacetylase activity, confirming the functionality of the complexes. Analysis of the BCL11B-NuRD association demonstrated that BCL11B directly interacted with the metastasis-associated proteins MTA1 and MTA2 through the amino-terminal region. We provide evidence for the functional requirement of MTA1 in transcriptional repression mediated by BCL11B through the following: (1) overexpression of MTA1 enhanced the transcriptional repression mediated by BCL11B, (2) knockdown of MTA1 expression by small interfering RNA inhibited BCL11B transcriptional repression activity and (3) MTA1 was specifically recruited to a BCL11B targeted promoter. Taken together, these data support the hypothesis that the NuRD complex mediates transcriptional repression function of BCL11B. (Less)
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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
transcriptional repression, BCL11B, NuRD
in
Oncogene
volume
24
issue
45
pages
6753 - 6764
publisher
Nature Publishing Group
external identifiers
  • pmid:16091750
  • scopus:27144528261
ISSN
1476-5594
DOI
10.1038/sj.onc.1208904
language
English
LU publication?
yes
id
0cc4ff09-b193-4e48-895f-bf8b2ab2d9c4 (old id 1134374)
date added to LUP
2016-04-01 12:31:04
date last changed
2022-07-30 03:51:04
@article{0cc4ff09-b193-4e48-895f-bf8b2ab2d9c4,
  abstract     = {{BCL11 genes play crucial roles in lymphopoiesis and have been associated with hematopoietic malignancies. Specifically, disruption of the BCL11B (B-cell chronic lymphocytic leukemia/lymphoma 11B) locus is linked to T-cell acute lymphoblastic leukemia, and the loss of heterozygosity in mice results in T-cell lymphoma. BCL11 proteins are related C2H2 zinc-finger transcription factors that act as transcriptional repressors. Here, we demonstrate the association of the endogenous BCL11B with the nucleosome remodeling and histone deacetylase (NuRD) complex, one of the major transcriptional corepressor complexes in mammalian cells. BCL11B complexes from T lymphocytes possess trichostatin A-sensitive histone deacetylase activity, confirming the functionality of the complexes. Analysis of the BCL11B-NuRD association demonstrated that BCL11B directly interacted with the metastasis-associated proteins MTA1 and MTA2 through the amino-terminal region. We provide evidence for the functional requirement of MTA1 in transcriptional repression mediated by BCL11B through the following: (1) overexpression of MTA1 enhanced the transcriptional repression mediated by BCL11B, (2) knockdown of MTA1 expression by small interfering RNA inhibited BCL11B transcriptional repression activity and (3) MTA1 was specifically recruited to a BCL11B targeted promoter. Taken together, these data support the hypothesis that the NuRD complex mediates transcriptional repression function of BCL11B.}},
  author       = {{Cismasiu, Valeriu and Adamo, Karen and Gecewicz, Jennifer and Duque, Javier and Lin, Qishan and Avram, Dorina}},
  issn         = {{1476-5594}},
  keywords     = {{transcriptional repression; BCL11B; NuRD}},
  language     = {{eng}},
  number       = {{45}},
  pages        = {{6753--6764}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Oncogene}},
  title        = {{BCL11B functionally associates with the NuRD complex in T lymphocytes to repress targeted promoter}},
  url          = {{http://dx.doi.org/10.1038/sj.onc.1208904}},
  doi          = {{10.1038/sj.onc.1208904}},
  volume       = {{24}},
  year         = {{2005}},
}