PMID- 12907736
OWN - NLM
STAT- MEDLINE
DCOM- 20040129
LR  - 20220224
IS  - 1362-4962 (Electronic)
IS  - 0305-1048 (Print)
IS  - 0305-1048 (Linking)
VI  - 31
IP  - 16
DP  - 2003 Aug 15
TI  - An important role for RUNX3 in human L1 transcription and retrotransposition.
PG  - 4929-40
AB  - LINE-1s (long interspersed nuclear elements-1) are abundant non-LTR 
      retrotransposons that comprise 17% of the human genome. The 5' untranslated 
      region (5'UTR) of human L1 (L1Hs) houses a poorly understood internal promoter. 
      Here we report that mutations at a putative runt-domain transcription factor 
      (RUNX) site (+83 to +101) in the 5'UTR decreased L1Hs transcription and 
      retrotransposition in cell culture-based assays. Exogenous expression of RUNX3, 
      but not the other two RUNX family members, RUNX1 and RUNX2, increased L1Hs 
      transcription and retrotransposition, which were otherwise decreased by siRNAs 
      targeting RUNX3 and a dominant negative RUNX. Further more, the specific 
      interaction between RUNX3 and its binding site was demonstrated by an 
      electrophoretic mobility shift assay (EMSA) using an anti-RUNX3 antibody. 
      Interestingly, RUNX3 may also regulate the antisense promoter activity of L1Hs 
      5'UTR via another putative RUNX site (+526 to +508), as revealed by site-directed 
      mutations and exogenous expression of RUNX factors. Our results indicate an 
      important role for RUNX3 in L1Hs retrotransposition as well as transcription from 
      its 5'UTR in both sense and antisense directions, and they should contribute to 
      our understanding of the mechanism underlying L1Hs retrotransposition and its 
      impact on the expression of adjacent cellular genes.
FAU - Yang, Nuo
AU  - Yang N
AD  - Department of Genetics, University of Pennsylvania School of Medicine, 
      Philadelphia, PA 19104, USA.
FAU - Zhang, Lin
AU  - Zhang L
FAU - Zhang, Yue
AU  - Zhang Y
FAU - Kazazian, Haig H Jr
AU  - Kazazian HH Jr
LA  - eng
GR  - R01 GM045398/GM/NIGMS NIH HHS/United States
GR  - GM 045398/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Nucleic Acids Res
JT  - Nucleic acids research
JID - 0411011
RN  - 0 (Core Binding Factor Alpha 3 Subunit)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Oligonucleotides)
RN  - 0 (RNA, Messenger)
RN  - 0 (Runx3 protein, human)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - 5' Flanking Region/genetics
MH  - Base Sequence
MH  - Binding Sites/genetics
MH  - Cell Line, Tumor
MH  - Core Binding Factor Alpha 3 Subunit
MH  - DNA-Binding Proteins/*genetics/metabolism/physiology
MH  - Electrophoretic Mobility Shift Assay
MH  - Gene Expression
MH  - HeLa Cells
MH  - Humans
MH  - Long Interspersed Nucleotide Elements/*genetics
MH  - *Mutagenesis, Insertional
MH  - Oligonucleotides/genetics/metabolism
MH  - Point Mutation
MH  - Promoter Regions, Genetic/genetics
MH  - Protein Binding
MH  - RNA Interference
MH  - RNA, Messenger/genetics/metabolism
MH  - Transcription Factors/*genetics/metabolism/physiology
MH  - *Transcription, Genetic
PMC - PMC169909
EDAT- 2003/08/09 05:00
MHDA- 2004/01/30 05:00
PMCR- 2003/08/15
CRDT- 2003/08/09 05:00
PHST- 2003/08/09 05:00 [pubmed]
PHST- 2004/01/30 05:00 [medline]
PHST- 2003/08/09 05:00 [entrez]
PHST- 2003/08/15 00:00 [pmc-release]
AID - gkg663 [pii]
AID - 10.1093/nar/gkg663 [doi]
PST - ppublish
SO  - Nucleic Acids Res. 2003 Aug 15;31(16):4929-40. doi: 10.1093/nar/gkg663.