PMID- 10488129
OWN - NLM
STAT- MEDLINE
DCOM- 19991104
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 39
DP  - 1999 Sep 24
TI  - In vivo structure of two divergent promoters at the human PCNA locus. Synthesis
      of antisense RNA and S phase-dependent binding of E2F complexes in intron 1.
PG  - 27829-38
AB  - Proliferating cell nuclear antigen (PCNA) synthesis is strictly regulated during 
      the cell cycle. To investigate PCNA transcriptional regulation, we have analyzed 
      protein-DNA interactions at the promoter region and in the first intron in
      quiescent fibroblasts and following serum stimulation. Twenty putative
      protein-binding sites, distributed in two divergent promoters at the PCNA locus, 
      were identified in vivo by genomic footprinting. These elements bind
      transcription factors continuously throughout the cell cycle with the exception
      of one E2F consensus site, located in the first intron at position +583. This E2F
      site becomes strongly occupied 18 h after serum stimulation, implying that an E2F
      activator complex plays a role in activation of the PCNA gene at the onset of S
      phase. We detected a 500-600-base pair-long antisense transcript by Northern blot
      analysis. This RNA has no apparent coding capacity and is constitutively
      transcribed from a promoter located within the first intron. We suggest that
      silencing of the PCNA gene is accomplished through base pairing between sense
      pre-mRNA and antisense RNA. The binding of S phase-specific E2F complexes at the 
      +583 element may help to overcome the negative effect of the antisense
      transcript, which results in up-regulation of PCNA expression in proliferating
      cells.
FAU - Tommasi, S
AU  - Tommasi S
AD  - Department of Biology, Beckman Research Institute, City of Hope National Medical 
      Center, Duarte, California 91010, USA. stomassi@smtplink.coh.org
FAU - Pfeifer, G P
AU  - Pfeifer GP
LA  - eng
GR  - ES06070/ES/NIEHS NIH HHS/United States
PT  - Journal Article
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 (Carrier Proteins)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (E2F Transcription Factors)
RN  - 0 (Proliferating Cell Nuclear Antigen)
RN  - 0 (RNA Precursors)
RN  - 0 (RNA, Antisense)
RN  - 0 (Retinoblastoma-Binding Protein 1)
RN  - 0 (Transcription Factor DP1)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Base Pairing
MH  - Base Sequence
MH  - *Carrier Proteins
MH  - Cell Cycle/*physiology
MH  - *Cell Cycle Proteins
MH  - Cells, Cultured
MH  - DNA Footprinting
MH  - *DNA-Binding Proteins
MH  - E2F Transcription Factors
MH  - Exons
MH  - Female
MH  - Fibroblasts/cytology/metabolism
MH  - *Gene Expression Regulation
MH  - *Genetic Variation
MH  - Humans
MH  - *Introns
MH  - Male
MH  - Molecular Sequence Data
MH  - Organ Specificity
MH  - Proliferating Cell Nuclear Antigen/*genetics
MH  - *Promoter Regions, Genetic
MH  - RNA Precursors/genetics/metabolism
MH  - RNA, Antisense/*genetics/metabolism
MH  - Retinoblastoma-Binding Protein 1
MH  - S Phase
MH  - Sequence Alignment
MH  - Skin/cytology/metabolism
MH  - Transcription Factor DP1
MH  - Transcription Factors/*metabolism
MH  - *Transcription, Genetic
EDAT- 1999/09/17 00:00
MHDA- 1999/09/17 00:01
CRDT- 1999/09/17 00:00
PHST- 1999/09/17 00:00 [pubmed]
PHST- 1999/09/17 00:01 [medline]
PHST- 1999/09/17 00:00 [entrez]
AID - 10.1074/jbc.274.39.27829 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Sep 24;274(39):27829-38. doi: 10.1074/jbc.274.39.27829.