PMID- 10318837
OWN - NLM
STAT- MEDLINE
DCOM- 19990617
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 20
DP  - 1999 May 14
TI  - Combinatorial interactions regulate cardiac expression of the murine
      adenylosuccinate synthetase 1 gene.
PG  - 14188-97
AB  - The mammalian heart begins contracting at the linear tube stage during
      embryogenesis and continuously pumps, nonstop, throughout the entire lifetime of 
      the animal. Therefore, the cardiac energy metabolizing pathways must be properly 
      established and efficiently functioning. While the biochemistry of these pathways
      is well defined, limited information regarding the regulation of cardiac
      metabolic genes is available. Previously, we reported that 1.9 kilobase pairs of 
      murine adenylosuccinate synthetase 1 gene (Adss1) 5'-flanking DNA directs high
      levels of reporter expression to the adult transgenic heart. In this report, we
      define the 1.9-kilobase pair fragment as a cardiac-specific enhancer that
      controls correct spatiotemporal expression of a reporter similar to the
      endogenous Adss1 gene. A 700-base pair fragment within this region activates a
      heterologous promoter specifically in adult transgenic hearts. Proteins present
      in a cardiac nuclear extract interact with potential transcription factor binding
      sites of this region and these cis-acting sites play important regulatory roles
      in the cardiac expression of this reporter. Finally, we report that several
      different cardiac transcription factors trans-activate the 1.9HSCAT construct
      through these sites and that combinations result in enhanced reporter expression.
      Adss1 appears to be one of the first target genes identified for the bHLH factors
      Hand1 and Hand2.
FAU - Lewis, A L
AU  - Lewis AL
AD  - Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, 
      Texas 77030, USA.
FAU - Xia, Y
AU  - Xia Y
FAU - Datta, S K
AU  - Datta SK
FAU - McMillin, J
AU  - McMillin J
FAU - Kellems, R E
AU  - Kellems RE
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Basic Helix-Loop-Helix Transcription Factors)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Hand1 protein, mouse)
RN  - 0 (Transcription Factors)
RN  - 0 (helix-loop-helix protein, eHAND)
RN  - EC 3.1.21.- (Deoxyribonuclease HindIII)
RN  - EC 3.1.21.- (endodeoxyribonuclease XBAI)
RN  - EC 3.1.21.4 (Deoxyribonucleases, Type II Site-Specific)
RN  - EC 6.3.4.4 (Adenylosuccinate Synthase)
SB  - IM
MH  - Adenylosuccinate Synthase/*genetics
MH  - Animals
MH  - Basic Helix-Loop-Helix Transcription Factors
MH  - DNA Mutational Analysis
MH  - DNA-Binding Proteins/metabolism
MH  - Deoxyribonuclease HindIII/metabolism
MH  - Deoxyribonucleases, Type II Site-Specific/metabolism
MH  - Gene Expression Regulation, Enzymologic
MH  - Genes, Reporter
MH  - Heart/embryology
MH  - Helix-Loop-Helix Motifs
MH  - In Situ Hybridization
MH  - Mice
MH  - Mice, Transgenic
MH  - Myocardial Contraction
MH  - Myocardium/*enzymology
MH  - Promoter Regions, Genetic
MH  - Transcription Factors/metabolism
MH  - Transcriptional Activation
EDAT- 1999/05/13 00:00
MHDA- 1999/05/13 00:01
CRDT- 1999/05/13 00:00
PHST- 1999/05/13 00:00 [pubmed]
PHST- 1999/05/13 00:01 [medline]
PHST- 1999/05/13 00:00 [entrez]
AID - 10.1074/jbc.274.20.14188 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 May 14;274(20):14188-97. doi: 10.1074/jbc.274.20.14188.