PMID- 17553693 OWN - NLM STAT- MEDLINE DCOM- 20070926 LR - 20181113 IS - 1044-7431 (Print) IS - 1095-9327 (Electronic) IS - 1044-7431 (Linking) VI - 35 IP - 3 DP - 2007 Jul TI - Ca2+, CREB and kruppel: a novel KLF7-binding element conserved in mouse and human TRKB promoters is required for CREB-dependent transcription. PG - 447-55 AB - Brain-derived neurotrophic factor (BDNF) signaling through its receptor, trkB, is essential for the proper development and function of the nervous system. Here we identify a novel regulatory element designated TCaRE3 (TRKB Ca(2+) response element 3) required for CREB-dependent TRKB transcription in neurons. TCaRE3-inactivating mutations abolished both Ca(2+)- and cAMP-stimulated TRKB expression, despite the presence of upstream CREs. TCaRE3 mutations also reduced basal expression by at least 80%. Electrophoretic mobility shift assays revealed the presence of a neuronal nuclear factor able to bind TCaRE3 in a sequence-specific manner and we have identified kruppel-like factor 7 (KLF7) as a candidate TCaRE3 transcription factor. Importantly, despite limited overall sequence homology between the promoter regions of the human and mouse TRKB genes, TCaRE3 exhibits 100% sequence identity. Mutation analysis of the human TRKB promoter region demonstrated that the role of TCaRE3 is also conserved, suggesting that the functional interaction between CREB bound to the CREs and KLF7 bound to TCaRE3 is essential for the proper regulation of TRKB in neurons. FAU - Kingsbury, Tami J AU - Kingsbury TJ AD - Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA. FAU - Krueger, Bruce K AU - Krueger BK LA - eng GR - R01NS048095/NS/NINDS NIH HHS/United States GR - K12 HD043489/HD/NICHD NIH HHS/United States GR - K12 HD43489/HD/NICHD NIH HHS/United States GR - R01 NS048095-02/NS/NINDS NIH HHS/United States GR - T32 NS07375/NS/NINDS NIH HHS/United States GR - T32 NS007375/NS/NINDS NIH HHS/United States GR - R01 NS048095-03/NS/NINDS NIH HHS/United States GR - R01 NS040492/NS/NINDS NIH HHS/United States GR - R01 NS048095-01A1/NS/NINDS NIH HHS/United States GR - R01 NS048095/NS/NINDS NIH HHS/United States GR - R01NS40492/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20070504 PL - United States TA - Mol Cell Neurosci JT - Molecular and cellular neurosciences JID - 9100095 RN - 0 (Cyclic AMP Response Element-Binding Protein) RN - 0 (Klf7 protein, mouse) RN - 0 (Kruppel-Like Transcription Factors) RN - 0 (RNA, Messenger) RN - EC 2.7.10.1 (Receptor, trkB) RN - SY7Q814VUP (Calcium) SB - IM MH - Animals MH - Calcium/*metabolism MH - Cells, Cultured MH - Cerebral Cortex/cytology MH - Chromatin Immunoprecipitation/methods MH - Cyclic AMP Response Element-Binding Protein/*physiology MH - Embryo, Mammalian MH - *Gene Expression Regulation MH - Humans MH - Kruppel-Like Transcription Factors/*metabolism MH - Mice MH - Mutation/physiology MH - Neurons/metabolism MH - Promoter Regions, Genetic/physiology MH - Protein Binding/physiology MH - RNA, Messenger/biosynthesis MH - Receptor, trkB/*metabolism MH - Reverse Transcriptase Polymerase Chain Reaction/methods MH - Signal Transduction MH - Transcription, Genetic MH - Transfection/methods PMC - PMC2042965 MID - NIHMS27294 EDAT- 2007/06/08 09:00 MHDA- 2007/09/27 09:00 PMCR- 2008/07/01 CRDT- 2007/06/08 09:00 PHST- 2006/12/10 00:00 [received] PHST- 2007/03/17 00:00 [revised] PHST- 2007/04/17 00:00 [accepted] PHST- 2007/06/08 09:00 [pubmed] PHST- 2007/09/27 09:00 [medline] PHST- 2007/06/08 09:00 [entrez] PHST- 2008/07/01 00:00 [pmc-release] AID - S1044-7431(07)00100-5 [pii] AID - 10.1016/j.mcn.2007.04.004 [doi] PST - ppublish SO - Mol Cell Neurosci. 2007 Jul;35(3):447-55. doi: 10.1016/j.mcn.2007.04.004. Epub 2007 May 4.