PMID- 10318857
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  - Genomic cloning and promoter analysis of aortic preferentially expressed gene-1. 
      Identification of a vascular smooth muscle-specific promoter mediated by an E box
      motif.
PG  - 14344-51
AB  - Aortic preferentially expressed gene-1 (APEG-1) was originally identified as a
      1.4-kilobase (kb) transcript preferentially expressed in differentiated vascular 
      smooth muscle cells (VSMC). Its expression is markedly down-regulated in
      de-differentiated VSMC, suggesting a role for APEG-1 in VSMC differentiation. We 
      have now determined that APEG-1 is a single-copy gene in the human, rat, and
      mouse genomes and have mapped human APEG-1 to chromosome 2q34. To study the
      molecular mechanisms regulating its expression, we characterized the genomic
      organization and promoter of mouse APEG-1. APEG-1 spans 4.5 kb in the mouse
      genome and is composed of five exons. Using reporter gene transfection analysis, 
      we found that a 2. 7-kb APEG-1 5'-flanking sequence directed a high level of
      promoter activity only in VSMC. Its activity was minimal in five other cell
      types. A repressor region located within an upstream 685-base pair sequence
      suppressed the activity of this 2.7-kb promoter. Further deletion and mutation
      analyses identified an E box motif as a positive regulatory element, which was
      bound by nuclear protein prepared from VSMC. In conjunction with its flanking
      sequence, this E box motif confers VSMC-specific enhancer activity to a
      heterologous SV40 promoter. To our knowledge, this is the first demonstration of 
      an E box motif that mediates gene expression restricted to VSMC.
FAU - Hsieh, C M
AU  - Hsieh CM
AD  - Cardiovascular Biology Laboratory, Harvard School of Public Health, Brigham and
      Women's Hospital, Boston, Massachusetts 02115, USA.
FAU - Yet, S F
AU  - Yet SF
FAU - Layne, M D
AU  - Layne MD
FAU - Watanabe, M
AU  - Watanabe M
FAU - Hong, A M
AU  - Hong AM
FAU - Perrella, M A
AU  - Perrella MA
FAU - Lee, M E
AU  - Lee ME
LA  - eng
GR  - F32-HL10113/HL/NHLBI NIH HHS/United States
GR  - KO8-HL03194/HL/NHLBI NIH HHS/United States
GR  - R01-GM53249/GM/NIGMS NIH HHS/United States
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 (Biomarkers)
RN  - 0 (Muscle Proteins)
RN  - 0 (Speg protein, rat)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (SPEG protein, human)
RN  - EC 2.7.11.1 (Speg protein, mouse)
RN  - EC 2.7.11.18 (Myosin-Light-Chain Kinase)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Base Sequence
MH  - Biomarkers
MH  - Cells, Cultured
MH  - Chromosomes, Human, Pair 2
MH  - Cloning, Molecular
MH  - Humans
MH  - Mice
MH  - Molecular Sequence Data
MH  - Muscle Proteins/*genetics
MH  - Muscle, Smooth, Vascular/*metabolism
MH  - Mutagenesis, Site-Directed
MH  - Myosin-Light-Chain Kinase
MH  - *Promoter Regions, Genetic
MH  - Protein-Serine-Threonine Kinases
MH  - Rats
MH  - Sequence Deletion
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.274.20.14344 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 May 14;274(20):14344-51. doi: 10.1074/jbc.274.20.14344.