PMID- 28860464
OWN - NLM
STAT- MEDLINE
DCOM- 20190611
LR  - 20190613
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 7
IP  - 1
DP  - 2017 Aug 31
TI  - Characterization of a core region in the A2UCOE that confers effective 
      anti-silencing activity.
PG  - 10213
LID - 10.1038/s41598-017-10222-3 [doi]
LID - 10213
AB  - We have previously shown that reliability of the A2UCOE in driving transgene 
      expression can be attributed to its resistance to DNA methylation, and its 
      ability to confer this property to linked regulatory sequences. In order to gain 
      a better understanding of how resistance to DNA methylation from the A2UCOE is 
      conferred, and whether the anti-silencing effect from the A2UCOE is confined 
      within a core region, we evaluated the anti-silencing effect of different 
      sub-domains. We found that maximal epigenetic regulatory activity was contained 
      within a 455 bp element derived from the CBX3 region when tested in the context 
      of a lentiviral vector in murine embryonic stem (ES) cells and human inducible 
      pluripotent stem (iPS) cells. This region possessed an active chromatin 
      signature, and operated effectively in cis to protect linked heterologous 
      regulatory elements from methylation, thereby conferring stable transgene 
      expression. Defined UCOE elements may be particularly useful for use in vectors 
      where gene expression is desired in methylation-prone chromatin environments such 
      as those encountered in pluripotent stem cells.
FAU - Zhang, Fang
AU  - Zhang F
AD  - Molecular and Cellular Immunology, UCL GOS Institute of Child Health, London, 
      WC1N 1EH, UK.
FAU - Santilli, Giorgia
AU  - Santilli G
AD  - Molecular and Cellular Immunology, UCL GOS Institute of Child Health, London, 
      WC1N 1EH, UK.
FAU - Thrasher, Adrian J
AU  - Thrasher AJ
AD  - Molecular and Cellular Immunology, UCL GOS Institute of Child Health, London, 
      WC1N 1EH, UK. a.thrasher@ucl.ac.uk.
LA  - eng
GR  - Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170831
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (CBX3 protein, human)
RN  - 0 (Chromosomal Proteins, Non-Histone)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Chromosomal Proteins, Non-Histone/*genetics
MH  - *CpG Islands
MH  - DNA Methylation
MH  - Epigenesis, Genetic
MH  - Gene Expression
MH  - Gene Silencing
MH  - HEK293 Cells
MH  - Humans
MH  - Induced Pluripotent Stem Cells/chemistry/cytology
MH  - Mice
MH  - Mouse Embryonic Stem Cells/chemistry/cytology
MH  - Promoter Regions, Genetic
MH  - *Transgenes
PMC - PMC5578987
COIS- The authors declare that they have no competing interests.
EDAT- 2017/09/02 06:00
MHDA- 2019/06/14 06:00
PMCR- 2017/08/31
CRDT- 2017/09/02 06:00
PHST- 2017/06/09 00:00 [received]
PHST- 2017/08/04 00:00 [accepted]
PHST- 2017/09/02 06:00 [entrez]
PHST- 2017/09/02 06:00 [pubmed]
PHST- 2019/06/14 06:00 [medline]
PHST- 2017/08/31 00:00 [pmc-release]
AID - 10.1038/s41598-017-10222-3 [pii]
AID - 10222 [pii]
AID - 10.1038/s41598-017-10222-3 [doi]
PST - epublish
SO  - Sci Rep. 2017 Aug 31;7(1):10213. doi: 10.1038/s41598-017-10222-3.