PMID- 12544823 OWN - NLM STAT- MEDLINE DCOM- 20030425 LR - 20231213 IS - 0959-4965 (Print) IS - 0959-4965 (Linking) VI - 14 IP - 1 DP - 2003 Jan 20 TI - Involvement of CLOCK:BMAL1 heterodimer in serum-responsive mPer1 induction. PG - 15-9 AB - A rapid induction of mouse period1 (mPer1) gene expression is supposed to be critical in the clock gene regulation, especially in the phase resetting of the clock, but its molecular mechanism is poorly understood. Based on the previous finding that the process does not involve de novo synthesis of proteins, we postulated the involvement of CLOCK:BMAL1 heterodimer, a positive regulator of circadian oscillator, in the rapid induction of mPer1 transcription. To test this hypothesis, we utilized CLOCKdelta19, a dominant-negative mutant, to suppress the function of CLOCK:BMAL1 in vitro. Serum-evoked rapid increases of mPer1 mRNA expression and promoter activity were significantly blunted when CLOCK:BMAL1 function was interfered with. Furthermore, DNA binding activity of CLOCK:BMAL1 heterodimer to five E-boxes of mPer1 promoter markedly increased shortly after serum shock. Taken together, these results suggest that CLOCK:BMAL1 heterodimer is not only a core component of negative feedback loop driving circadian oscillator, but also involved in the rapid induction of mPer1during phase resetting of the clock. CI - Copyright 2003 Lippincott Williams & Wilkins FAU - Jung, Hosung AU - Jung H AD - Development and Neuroendocrine Research Laboratory, School of Biomedical Sciences, Seoul National University, Korea. FAU - Choe, Youngshik AU - Choe Y FAU - Kim, Hyunjung AU - Kim H FAU - Park, Noheon AU - Park N FAU - Son, Gi Hoon AU - Son GH FAU - Khang, Inkoo AU - Khang I FAU - Kim, Kyungjin AU - Kim K LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Neuroreport JT - Neuroreport JID - 9100935 RN - 0 (ARNTL Transcription Factors) RN - 0 (Bmal1 protein, mouse) RN - 0 (Basic Helix-Loop-Helix Transcription Factors) RN - 0 (Cell Cycle Proteins) RN - 0 (Culture Media, Serum-Free) RN - 0 (Nuclear Proteins) RN - 0 (Per1 protein, mouse) RN - 0 (Period Circadian Proteins) RN - 0 (Proto-Oncogene Proteins c-fos) RN - 0 (RNA, Messenger) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Trans-Activators) RN - 0 (Transcription Factors) RN - 9007-49-2 (DNA) RN - EC 1.13.12.- (Luciferases) RN - EC 2.3.1.48 (CLOCK Proteins) RN - EC 2.3.1.48 (Clock protein, mouse) SB - IM MH - 3T3 Cells/drug effects MH - ARNTL Transcription Factors MH - Alleles MH - Animals MH - Basic Helix-Loop-Helix Transcription Factors MH - CLOCK Proteins MH - Cattle MH - Cell Cycle Proteins MH - Circadian Rhythm/*physiology MH - Culture Media, Serum-Free/pharmacology MH - DNA/genetics/metabolism MH - Dimerization MH - Feedback, Physiological MH - Fetal Blood/physiology MH - Gene Expression Regulation/*physiology MH - Genes, Dominant MH - Genes, Reporter MH - Genes, fos MH - Luciferases/biosynthesis/genetics MH - Mice MH - Nuclear Proteins/*biosynthesis/genetics MH - Period Circadian Proteins MH - Promoter Regions, Genetic MH - Proto-Oncogene Proteins c-fos/biosynthesis MH - RNA, Messenger/biosynthesis MH - Recombinant Fusion Proteins/physiology MH - Trans-Activators/chemistry/genetics/*physiology MH - Transcription Factors/chemistry/*physiology MH - Transfection EDAT- 2003/01/25 04:00 MHDA- 2003/04/26 05:00 CRDT- 2003/01/25 04:00 PHST- 2003/01/25 04:00 [pubmed] PHST- 2003/04/26 05:00 [medline] PHST- 2003/01/25 04:00 [entrez] AID - 10.1097/00001756-200301200-00003 [doi] PST - ppublish SO - Neuroreport. 2003 Jan 20;14(1):15-9. doi: 10.1097/00001756-200301200-00003.