Regulation of a Cell Type-specific Silencer in the Human Interleukin-3 Gene Promoter by the Transcription Factor YY1 and an AP2 Sequence-recognizing Factor

Negative regulation of cytokine gene transcription is an important mechanism in maintaining homeostasis of immune function. In this study, we characterized a silencer element in the human interleukin-3 gene promoter that is responsible for the cell-specific expression of interleukin-3. This silencer...

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Veröffentlicht in:The Journal of biological chemistry 1999-09, Vol.274 (38), p.26661-26667
Hauptverfasser: Ye, Jianping, Young, Howard A., Zhang, Xiaoying, Castranova, Vince, Vallyathan, Val, Shi, Xianglin
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container_end_page 26667
container_issue 38
container_start_page 26661
container_title The Journal of biological chemistry
container_volume 274
creator Ye, Jianping
Young, Howard A.
Zhang, Xiaoying
Castranova, Vince
Vallyathan, Val
Shi, Xianglin
description Negative regulation of cytokine gene transcription is an important mechanism in maintaining homeostasis of immune function. In this study, we characterized a silencer element in the human interleukin-3 gene promoter that is responsible for the cell-specific expression of interleukin-3. This silencer activity was proposed to be mediated by an unidentified nuclear inhibitory protein (NIP). In this study, we have identified two nuclear factors that are responsible for the silencer activity in T cells. The NIP element forms four specific DNA-protein complexes (designated as complexes A–D) with the Jurkat nuclear proteins. Complex A contains a nuclear protein that shares DNA-binding specificity with the transcription factor AP2 (designated as an AP2 sequence-recognizing factor (ASRF)). Formation of this ASRF complex is required for the NIP silencer function, as mutation of the ASRF-binding site abrogated the silencer activity. Complex B contains the nuclear factor YY1 (Yin-Yang 1), whose function is to down-regulate ASRF activity in the silencer. YY1 activity is supported by data from mutation and cotransfection analyses. Complexes C and D are formed by nonspecific binding proteins and do not express any regulatory activity in the NIP element. These data indicate that a cell type-specific silencer activity might be determined by a unique profile of ubiquitous transcription factors.
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In this study, we characterized a silencer element in the human interleukin-3 gene promoter that is responsible for the cell-specific expression of interleukin-3. This silencer activity was proposed to be mediated by an unidentified nuclear inhibitory protein (NIP). In this study, we have identified two nuclear factors that are responsible for the silencer activity in T cells. The NIP element forms four specific DNA-protein complexes (designated as complexes A–D) with the Jurkat nuclear proteins. Complex A contains a nuclear protein that shares DNA-binding specificity with the transcription factor AP2 (designated as an AP2 sequence-recognizing factor (ASRF)). Formation of this ASRF complex is required for the NIP silencer function, as mutation of the ASRF-binding site abrogated the silencer activity. Complex B contains the nuclear factor YY1 (Yin-Yang 1), whose function is to down-regulate ASRF activity in the silencer. 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In this study, we characterized a silencer element in the human interleukin-3 gene promoter that is responsible for the cell-specific expression of interleukin-3. This silencer activity was proposed to be mediated by an unidentified nuclear inhibitory protein (NIP). In this study, we have identified two nuclear factors that are responsible for the silencer activity in T cells. The NIP element forms four specific DNA-protein complexes (designated as complexes A–D) with the Jurkat nuclear proteins. Complex A contains a nuclear protein that shares DNA-binding specificity with the transcription factor AP2 (designated as an AP2 sequence-recognizing factor (ASRF)). Formation of this ASRF complex is required for the NIP silencer function, as mutation of the ASRF-binding site abrogated the silencer activity. Complex B contains the nuclear factor YY1 (Yin-Yang 1), whose function is to down-regulate ASRF activity in the silencer. 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source MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection
subjects AP2 sequence-recognizing factor
DNA-Binding Proteins - metabolism
Electrophoresis, Polyacrylamide Gel
Erythroid-Specific DNA-Binding Factors
Gene Expression Regulation
Humans
Interleukin-3 - genetics
Jurkat Cells
nuclear inhibitory protein
Promoter Regions, Genetic
Repressor Proteins - genetics
Transcription Factor AP-2
transcription factor YY1
Transcription Factors - metabolism
YY1 protein
YY1 Transcription Factor
title Regulation of a Cell Type-specific Silencer in the Human Interleukin-3 Gene Promoter by the Transcription Factor YY1 and an AP2 Sequence-recognizing Factor
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