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A repressor complex, AP4 transcription factor and geminin, negatively regulates expression of target genes in nonneuronal cells

Authors
 Mi-Young Kim  ;  Byung Chul Jeong  ;  Ji Hee Lee  ;  Hae Jin Kee  ;  Hyun Kook  ;  Nack Sung Kim  ;  Yoon Ha Kim  ;  Jong-Keun Kim  ;  Kyu Youn Ahn  ;  Kyung Keun Kim 
Citation
 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol.103(35) : 13074-13079, 2006 
Journal Title
 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 
ISSN
 0027-8424 
Issue Date
2006
MeSH
Animals ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ; Carrier Proteins/genetics ; Carrier Proteins/metabolism ; Cell Cycle Proteins/metabolism* ; Cerebral Cortex/cytology ; Cerebral Cortex/drug effects ; Cerebral Cortex/metabolism ; Cerebral Cortex/pathology ; DNA-Binding Proteins/metabolism* ; Down Syndrome/genetics ; Down-Regulation/drug effects ; Down-Regulation/genetics* ; Fetus/metabolism ; Geminin ; Gene Expression Regulation, Developmental/drug effects ; Genes, Reporter ; Histone Deacetylases/metabolism ; Humans ; Hydroxamic Acids/pharmacology ; Mice ; Nerve Tissue Proteins/genetics ; Nerve Tissue Proteins/metabolism ; Neurons/metabolism* ; Nuclear Receptor Co-Repressor 2 ; Promoter Regions, Genetic/genetics ; Protein Binding/drug effects ; Protein-Serine-Threonine Kinases/metabolism ; Protein-Tyrosine Kinases ; Repressor Proteins/metabolism* ; Transcription, Genetic/drug effects ; beta-Galactosidase/metabolism
Abstract
The transcription of neuron-specific genes must be repressed in nonneuronal cells. REST/NRSF is a transcription factor that restricts the expression of many neuronal genes through interaction with the neuron-restrictive silencer element at the promoter level. PAHX-AP1 is a neuronal gene that is developmentally up-regulated in the adult mouse brain but that has no functional NRSE motif in its 5' upstream sequence. Here, we report that the transcription factor AP4 and the corepressor geminin form a functional complex in which SMRT and histone deacetylase 3 are recruited. The functional complex represses PAHX-AP1 expression in nonneuronal cells and participates in regulating the developmental expression of PAHX-AP1 in the brain. This complex also serves as a transcriptional repressor of DYRK1A, a candidate gene for Down's syndrome. Furthermore, compared with that in normal fetal brain, the expression of AP4 and geminin is reduced in Down's syndrome fetal brain at 20 weeks of gestation age, at which time premature overexpression of dual-specificity tyrosine-phosphorylated and regulated kinase 1A (DYRK1A) is observed. Our findings indicate that AP4 and geminin act as a previously undescribed repressor complex distinct from REST/NRSF to negatively regulate the expression of target genes in nonneuronal cells and suggest that the AP4-geminin complex may contribute to suppressing the precocious expression of target genes in fetal brain
Files in This Item:
T200605427.pdf Download
DOI
10.1073/pnas.0601915103
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Mi Young(김미영)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/111115
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