PMID- 25825708
OWN - NLM
STAT- MEDLINE
DCOM- 20150724
LR  - 20181113
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 112
IP  - 15
DP  - 2015 Apr 14
TI  - SOX2 primes the epigenetic landscape in neural precursors enabling proper gene 
      activation during hippocampal neurogenesis.
PG  - E1936-45
LID - 10.1073/pnas.1421480112 [doi]
AB  - Newborn granule neurons generated from neural progenitor cells (NPCs) in the 
      adult hippocampus play a key role in spatial learning and pattern separation. 
      However, the molecular mechanisms that control activation of their neurogenic 
      program remain poorly understood. Here, we report a novel function for the 
      pluripotency factor sex-determining region Y (SRY)-related HMG box 2 (SOX2) in 
      regulating the epigenetic landscape of poised genes activated at the onset of 
      neuronal differentiation. We found that SOX2 binds to bivalently marked promoters 
      of poised proneural genes [neurogenin 2 (Ngn2) and neurogenic differentiation 1 
      (NeuroD1)] and a subset of neurogenic genes [e.g., SRY-box 21 (Sox21), 
      brain-derived neurotrophic factor (Bdnf), and growth arrest and 
      DNA-damage-inducible, beta (Gadd45b)] where it functions to maintain the bivalent 
      chromatin state by preventing excessive polycomb repressive complex 2 activity. 
      Conditional ablation of SOX2 in adult hippocampal NPCs impaired the activation of 
      proneural and neurogenic genes, resulting in increased neuroblast death and 
      functionally aberrant newborn neurons. We propose that SOX2 sets a permissive 
      epigenetic state in NPCs, thus enabling proper activation of the neuronal 
      differentiation program under neurogenic cue.
FAU - Amador-Arjona, Alejandro
AU  - Amador-Arjona A
AD  - Center for Neuroscience, Aging, and Stem Cell Research, Sanford-Burnham Medical 
      Research Institute, La Jolla, CA 92037; and.
FAU - Cimadamore, Flavio
AU  - Cimadamore F
AD  - Center for Neuroscience, Aging, and Stem Cell Research, Sanford-Burnham Medical 
      Research Institute, La Jolla, CA 92037; and.
FAU - Huang, Chun-Teng
AU  - Huang CT
AD  - Center for Neuroscience, Aging, and Stem Cell Research, Sanford-Burnham Medical 
      Research Institute, La Jolla, CA 92037; and.
FAU - Wright, Rebecca
AU  - Wright R
AD  - Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA 
      92037.
FAU - Lewis, Susan
AU  - Lewis S
AD  - Center for Neuroscience, Aging, and Stem Cell Research, Sanford-Burnham Medical 
      Research Institute, La Jolla, CA 92037; and.
FAU - Gage, Fred H
AU  - Gage FH
AD  - Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA 
      92037.
FAU - Terskikh, Alexey V
AU  - Terskikh AV
AD  - Center for Neuroscience, Aging, and Stem Cell Research, Sanford-Burnham Medical 
      Research Institute, La Jolla, CA 92037; and terskikh@burnham.org.
LA  - eng
GR  - R01 NS066278/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 - 20150330
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Basic Helix-Loop-Helix Transcription Factors)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Neurod1 protein, mouse)
RN  - 0 (Neurog2 protein, mouse)
RN  - 0 (SOXB1 Transcription Factors)
RN  - 0 (Sox2 protein, mouse)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Basic Helix-Loop-Helix Transcription Factors/genetics/metabolism
MH  - Blotting, Western
MH  - Cell Cycle/genetics
MH  - Cell Proliferation/genetics
MH  - Cells, Cultured
MH  - *Epigenesis, Genetic
MH  - Gene Expression
MH  - Hippocampus/cytology/metabolism
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Microscopy, Fluorescence
MH  - Nerve Tissue Proteins/genetics/metabolism
MH  - Neural Stem Cells/*metabolism
MH  - Neurogenesis/*genetics
MH  - Neurons/metabolism/physiology
MH  - Patch-Clamp Techniques
MH  - Promoter Regions, Genetic/genetics
MH  - Protein Binding
MH  - RNA Interference
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - SOXB1 Transcription Factors/deficiency/*genetics/metabolism
MH  - *Transcriptional Activation
PMC - PMC4403144
OTO - NOTNLM
OT  - SOX2
OT  - epigenetics
OT  - neurogenesis
COIS- The authors declare no conflict of interest.
EDAT- 2015/04/01 06:00
MHDA- 2015/07/25 06:00
PMCR- 2015/10/14
CRDT- 2015/04/01 06:00
PHST- 2015/04/01 06:00 [entrez]
PHST- 2015/04/01 06:00 [pubmed]
PHST- 2015/07/25 06:00 [medline]
PHST- 2015/10/14 00:00 [pmc-release]
AID - 1421480112 [pii]
AID - 201421480 [pii]
AID - 10.1073/pnas.1421480112 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2015 Apr 14;112(15):E1936-45. doi: 
      10.1073/pnas.1421480112. Epub 2015 Mar 30.