Document Detail

Transcription factor NF-Y is a functional regulator of the transcription of core clock gene Bmal1.
MedLine Citation:
PMID:  24030830     Owner:  NLM     Status:  MEDLINE    
The circadian clock enables organisms to adjust to daily environmental changes and synchronize multiple molecular, biochemical, physiological, and behavioral processes accordingly. In mammalian clock work, Bmal1 is the most important core clock gene, which works with another core clock gene Clock to drive the expression of other clock genes and clock-controlled genes. However, the regulation of Bmal1 has not been fully understood. This work was aimed at identifying the positive regulator(s) of Bmal1 transcription. A series of 5' deletion reporter constructs was generated, and binding site mutations of mouse Bmal1 promoter fragments were cloned into pGL3-basic and pGL3(R2.1)-basic plasmids and transfected into NIH 3T3 cells. Luciferase activity was either measured 48 h after transfection or recorded for 4 days after serum shock. DNA affinity precipitation assay was used to detect the transcription factors binding to Bmal1 promoter. Small interfering RNA against nuclear factor Y, subunit A (NF-YA) and dominant negative NF-YA were employed to study the role of NF-Y in Bmal1 transcription regulation. Deletion and mutation analyses identified two clusters of CCAAT/GC-boxes at the proximal region of Bmal1 promoter as the activating cis-elements. Bmal1 promoter activity was up-regulated by NF-Y and/or Sp1 and repressed by dominant negative NF-YA or siRNA against NF-YA. The activation of Bmal1 promoter activity by NF-Y and Sp1 was inhibited by Rev-Erbα. DNA affinity precipitation assay showed that NF-Y and Sp1 bound to the two CCAAT/GC clusters of Bmal1 promoter. These results indicate that NF-Y is a functional activator of Bmal1 transcription and it cooperates with Sp1 and Rev-Erbα to generate the daily cycle of Bmal1 expression.
Jun Xiao; Yongchun Zhou; Hao Lai; Shi Lei; Lisa H Chi; Xianwei Mo
Publication Detail:
Type:  Journal Article     Date:  2013-09-12
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  288     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2013 Nov 
Date Detail:
Created Date:  2013-11-04     Completed Date:  2013-12-31     Revised Date:  2014-11-04    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  31930-6     Citation Subset:  IM    
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MeSH Terms
ARNTL Transcription Factors / biosynthesis*,  genetics
CCAAT-Binding Factor / genetics,  metabolism*
Circadian Clocks / physiology*
Gene Expression Regulation / physiology*
NIH 3T3 Cells
Oncogene Proteins v-erbA / genetics,  metabolism
RNA, Small Interfering / genetics
Response Elements / physiology*
Sp1 Transcription Factor / genetics,  metabolism
Transcription, Genetic / physiology*
Reg. No./Substance:
0/ARNTL Transcription Factors; 0/Arntl protein, mouse; 0/CCAAT-Binding Factor; 0/Nfya protein, mouse; 0/Oncogene Proteins v-erbA; 0/RNA, Small Interfering; 0/Sp1 Transcription Factor

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