PMID- 28594324
OWN - NLM
STAT- MEDLINE
DCOM- 20180308
LR  - 20230804
IS  - 2050-084X (Electronic)
IS  - 2050-084X (Linking)
VI  - 6
DP  - 2017 Jun 8
TI  - MeCP2 regulates Tet1-catalyzed demethylation, CTCF binding, and 
      learning-dependent alternative splicing of the BDNF gene in Turtle.
LID - e25384 [pii]
LID - 10.7554/eLife.25384 [doi]
AB  - MECP2 mutations underlying Rett syndrome cause widespread misregulation of gene 
      expression. Functions for MeCP2 other than transcriptional are not well 
      understood. In an ex vivo brain preparation from the pond turtle Trachemys 
      scripta elegans, an intraexonic splicing event in the brain-derived neurotrophic 
      factor (BDNF) gene generates a truncated mRNA transcript in naive brain that is 
      suppressed upon classical conditioning. MeCP2 and its partners, splicing factor 
      Y-box binding protein 1 (YB-1) and methylcytosine dioxygenase 1 (Tet1), bind to 
      BDNF chromatin in naive but dissociate during conditioning; the dissociation 
      correlating with decreased DNA methylation. Surprisingly, conditioning results in 
      new occupancy of BDNF chromatin by DNA insulator protein CCCTC-binding factor 
      (CTCF), which is associated with suppression of splicing in conditioning. 
      Knockdown of MeCP2 shows it is instrumental for splicing and inhibits Tet1 and 
      CTCF binding thereby negatively impacting DNA methylation and 
      conditioning-dependent splicing regulation. Thus, mutations in MECP2 can have 
      secondary effects on DNA methylation and alternative splicing.
FAU - Zheng, Zhaoqing
AU  - Zheng Z
AD  - Neuroscience Group, Basic Biomedical Sciences, University of South Dakota, 
      Sanford School of Medicine, Vermillion, United States.
FAU - Ambigapathy, Ganesh
AU  - Ambigapathy G
AUID- ORCID: 0000-0002-4491-8513
AD  - Neuroscience Group, Basic Biomedical Sciences, University of South Dakota, 
      Sanford School of Medicine, Vermillion, United States.
FAU - Keifer, Joyce
AU  - Keifer J
AUID- ORCID: 0000-0002-5900-0414
AD  - Neuroscience Group, Basic Biomedical Sciences, University of South Dakota, 
      Sanford School of Medicine, Vermillion, United States.
LA  - eng
GR  - R01 NS051187/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20170608
PL  - England
TA  - Elife
JT  - eLife
JID - 101579614
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Chromatin)
RN  - 0 (Methyl-CpG-Binding Protein 2)
RN  - 0 (Y-Box-Binding Protein 1)
RN  - 9007-49-2 (DNA)
RN  - EC 1.- (Mixed Function Oxygenases)
SB  - IM
MH  - *Alternative Splicing
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*biosynthesis/genetics
MH  - Chromatin/metabolism
MH  - Conditioning, Classical
MH  - DNA/metabolism
MH  - Demethylation
MH  - *Learning
MH  - Methyl-CpG-Binding Protein 2/*metabolism
MH  - Mixed Function Oxygenases/*metabolism
MH  - Protein Binding
MH  - Turtles/*physiology
MH  - Y-Box-Binding Protein 1/metabolism
PMC - PMC5481183
OTO - NOTNLM
OT  - BDNF
OT  - MeCP2
OT  - Rett syndrome
OT  - Tet1
OT  - alternative splicing
OT  - conditioning
OT  - neuroscience
COIS- The authors declare that no competing interests exist.
EDAT- 2017/06/09 06:00
MHDA- 2018/03/09 06:00
PMCR- 2017/06/09
CRDT- 2017/06/09 06:00
PHST- 2017/01/23 00:00 [received]
PHST- 2017/06/07 00:00 [accepted]
PHST- 2017/06/09 06:00 [pubmed]
PHST- 2018/03/09 06:00 [medline]
PHST- 2017/06/09 06:00 [entrez]
PHST- 2017/06/09 00:00 [pmc-release]
AID - e25384 [pii]
AID - 25384 [pii]
AID - 10.7554/eLife.25384 [doi]
PST - epublish
SO  - Elife. 2017 Jun 8;6:e25384. doi: 10.7554/eLife.25384.