PMID- 14580376
OWN - NLM
STAT- MEDLINE
DCOM- 20040715
LR  - 20190922
IS  - 0143-4004 (Print)
IS  - 0143-4004 (Linking)
VI  - 24
IP  - 10
DP  - 2003 Nov
TI  - Oxygen-regulated expression of TGF-beta 3, a growth factor involved in 
      trophoblast differentiation.
PG  - 941-50
AB  - The transforming growth factor-beta 3 (TGF-beta 3) is involved in 
      oxygen-dependent differentiation processes during placental development and 
      pregnancy disorders. However, the importance of oxygen partial pressure for the 
      regulation of TGF-beta 3 expression is presently unclear. We and others presented 
      preliminary evidence that the hypoxia-inducible factor-1 (HIF-1) confers TGF-beta 
      3 transcription but it was unknown whether this occurred directly or indirectly. 
      To analyze how HIF-1 regulates TGF-beta 3 gene transcription, we cloned and 
      sequenced the mouse TGF-beta 3 promoter region. Multiple putative HIF-1 binding 
      sites (HBSs) were identified, many of which co-localized with two G+C rich CpG 
      islands 5' to the TGF-beta 3 transcription start site. A 6.8 kb fragment of the 
      TGF-beta 3 promoter induced reporter gene expression under hypoxic conditions or 
      when treated with an iron chelator known to stabilize and activate the HIF-1 
      alpha subunit. Deletion of a 2.4 kb fragment upstream of the distal CpG island 
      abolished inducibility of reporter gene expression. Two HBSs (HBS1 and HBS6) that 
      bound the HIF-1 protein could be identified within this 2.4 kb fragment. These 
      results suggest that TGF-beta 3 gene expression is directly regulated by HIF-1.
FAU - Schaffer, L
AU  - Schaffer L
AD  - Department of Obstetrics and Perinatal Physiology, University Hospital Zurich, 
      Zurich, Switzerland.
FAU - Scheid, A
AU  - Scheid A
FAU - Spielmann, P
AU  - Spielmann P
FAU - Breymann, C
AU  - Breymann C
FAU - Zimmermann, R
AU  - Zimmermann R
FAU - Meuli, M
AU  - Meuli M
FAU - Gassmann, M
AU  - Gassmann M
FAU - Marti, H H
AU  - Marti HH
FAU - Wenger, R H
AU  - Wenger RH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Placenta
JT  - Placenta
JID - 8006349
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Hif1a protein, mouse)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Nuclear Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tgfb3 protein, mouse)
RN  - 0 (Transcription Factors)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (Transforming Growth Factor beta3)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Animals
MH  - Binding Sites
MH  - Cell Differentiation
MH  - Cell Hypoxia
MH  - DNA/metabolism
MH  - DNA-Binding Proteins/*physiology
MH  - Female
MH  - Gene Expression Regulation
MH  - Hypoxia-Inducible Factor 1
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Mice
MH  - Nuclear Proteins/*physiology
MH  - Pregnancy
MH  - Promoter Regions, Genetic
MH  - RNA, Messenger/metabolism
MH  - *Transcription Factors
MH  - *Transcriptional Activation
MH  - Transforming Growth Factor beta/*genetics/metabolism/physiology
MH  - Transforming Growth Factor beta3
MH  - Trophoblasts/cytology
EDAT- 2003/10/29 05:00
MHDA- 2004/07/16 05:00
CRDT- 2003/10/29 05:00
PHST- 2003/10/29 05:00 [pubmed]
PHST- 2004/07/16 05:00 [medline]
PHST- 2003/10/29 05:00 [entrez]
AID - S0143400403001668 [pii]
AID - 10.1016/s0143-4004(03)00166-8 [doi]
PST - ppublish
SO  - Placenta. 2003 Nov;24(10):941-50. doi: 10.1016/s0143-4004(03)00166-8.