Inhibition of p300/CBP by early B-cell factor
(2003) In Molecular and Cellular Biology 23(11). p.3837-3846- Abstract
- Early B-cell factor (EBF) is a DNA binding protein required for early B-cell development. It activates transcription of several B-cell-specific genes, including the {lambda}5 gene, which encodes a protein necessary for signaling by the pre-B-cell receptor. In an effort to understand the mechanism by which EBF activates transcription, we examined its interaction with the coactivator protein p300/CBP. We found that two domains of EBF each bind the histone acetyltransferase (HAT)/CH3 domain of p300/CBP both in vitro and in vivo. Surprisingly, transcriptional activation by EBF was not sensitive to E1A, a potent p300/CBP inhibitor. In fact, overexpressed EBF mimicked E1A by severely repressing the activity of several other transcription... (More)
- Early B-cell factor (EBF) is a DNA binding protein required for early B-cell development. It activates transcription of several B-cell-specific genes, including the {lambda}5 gene, which encodes a protein necessary for signaling by the pre-B-cell receptor. In an effort to understand the mechanism by which EBF activates transcription, we examined its interaction with the coactivator protein p300/CBP. We found that two domains of EBF each bind the histone acetyltransferase (HAT)/CH3 domain of p300/CBP both in vitro and in vivo. Surprisingly, transcriptional activation by EBF was not sensitive to E1A, a potent p300/CBP inhibitor. In fact, overexpressed EBF mimicked E1A by severely repressing the activity of several other transcription factors, including E47, a protein that acts cooperatively with EBF to promote transcription of the {lambda}5 gene. This broad inhibitory profile correlated with EBF's ability to repress the HAT activity of p300/CBP in vivo and in vitro. However, such a repressed complex is not likely to form at the {lambda}5 promoter in vivo since (i) EBF could not bind p300/CBP and DNA simultaneously and (ii) the cooperativity imparted by E47 was sensitive to E1A. Our data reveal an intriguing inhibitory property of EBF—a property shared only by E1A, Twist, Pu.1, and the Hox family of homeodomain proteins—and suggest that E47 and EBF play distinct roles during {lambda}5 promoter activation. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/141935
- author
- Zhao, Fang ; McCarrick-Walmsley, Ruth ; Åkerblad, Peter ; Sigvardsson, Mikael LU and Kadesch, Tom
- organization
- publishing date
- 2003
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Molecular and Cellular Biology
- volume
- 23
- issue
- 11
- pages
- 3837 - 3846
- publisher
- American Society for Microbiology
- external identifiers
-
- wos:000183031900011
- pmid:12748286
- scopus:0037570593
- ISSN
- 0270-7306
- DOI
- 10.1128/MCB.23.11.3837-3846.2003
- language
- English
- LU publication?
- yes
- id
- 6c98d4a1-a57f-4913-b140-e3330eac3a2f (old id 141935)
- alternative location
- http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12748286&query_hl=39
- date added to LUP
- 2016-04-01 12:10:47
- date last changed
- 2022-07-29 23:19:54
@article{6c98d4a1-a57f-4913-b140-e3330eac3a2f, abstract = {{Early B-cell factor (EBF) is a DNA binding protein required for early B-cell development. It activates transcription of several B-cell-specific genes, including the {lambda}5 gene, which encodes a protein necessary for signaling by the pre-B-cell receptor. In an effort to understand the mechanism by which EBF activates transcription, we examined its interaction with the coactivator protein p300/CBP. We found that two domains of EBF each bind the histone acetyltransferase (HAT)/CH3 domain of p300/CBP both in vitro and in vivo. Surprisingly, transcriptional activation by EBF was not sensitive to E1A, a potent p300/CBP inhibitor. In fact, overexpressed EBF mimicked E1A by severely repressing the activity of several other transcription factors, including E47, a protein that acts cooperatively with EBF to promote transcription of the {lambda}5 gene. This broad inhibitory profile correlated with EBF's ability to repress the HAT activity of p300/CBP in vivo and in vitro. However, such a repressed complex is not likely to form at the {lambda}5 promoter in vivo since (i) EBF could not bind p300/CBP and DNA simultaneously and (ii) the cooperativity imparted by E47 was sensitive to E1A. Our data reveal an intriguing inhibitory property of EBF—a property shared only by E1A, Twist, Pu.1, and the Hox family of homeodomain proteins—and suggest that E47 and EBF play distinct roles during {lambda}5 promoter activation.}}, author = {{Zhao, Fang and McCarrick-Walmsley, Ruth and Åkerblad, Peter and Sigvardsson, Mikael and Kadesch, Tom}}, issn = {{0270-7306}}, language = {{eng}}, number = {{11}}, pages = {{3837--3846}}, publisher = {{American Society for Microbiology}}, series = {{Molecular and Cellular Biology}}, title = {{Inhibition of p300/CBP by early B-cell factor}}, url = {{https://lup.lub.lu.se/search/files/2814746/624799.pdf}}, doi = {{10.1128/MCB.23.11.3837-3846.2003}}, volume = {{23}}, year = {{2003}}, }