PMID- 29254825
OWN - NLM
STAT- MEDLINE
DCOM- 20190130
LR  - 20190301
IS  - 1095-9327 (Electronic)
IS  - 1044-7431 (Print)
IS  - 1044-7431 (Linking)
VI  - 87
DP  - 2018 Mar
TI  - The histone demethylase Kdm6b regulates a mature gene expression program in 
      differentiating cerebellar granule neurons.
PG  - 4-17
LID - S1044-7431(17)30243-9 [pii]
LID - 10.1016/j.mcn.2017.11.005 [doi]
AB  - The histone H3 lysine 27 (H3K27) demethylase Kdm6b (Jmjd3) can promote cellular 
      differentiation, however its physiological functions in neurons remain to be 
      fully determined. We studied the expression and function of Kdm6b in 
      differentiating granule neurons of the developing postnatal mouse cerebellum. At 
      postnatal day 7, Kdm6b is expressed throughout the layers of the developing 
      cerebellar cortex, but its expression is upregulated in newborn cerebellar 
      granule neurons (CGNs). Atoh1-Cre mediated conditional knockout of Kdm6b in CGN 
      precursors either alone or in combination with Kdm6a did not disturb the gross 
      morphological development of the cerebellum. Furthermore, RNAi-mediated knockdown 
      of Kdm6b in cultured CGN precursors did not alter the induced expression of early 
      neuronal marker genes upon cell cycle exit. By contrast, knockdown of Kdm6b 
      significantly impaired the induction of a mature neuronal gene expression 
      program, which includes gene products required for functional synapse maturation. 
      Loss of Kdm6b also impaired the ability of Brain-Derived Neurotrophic Factor 
      (BDNF) to induce expression of Grin2c and Tiam1 in maturing CGNs. Taken together, 
      these data reveal a previously unknown role for Kdm6b in the postmitotic stages 
      of CGN maturation and suggest that Kdm6b may work, at least in part, by a 
      transcriptional mechanism that promotes gene sensitivity to regulation by BDNF.
CI  - Copyright (c) 2017 Elsevier Inc. All rights reserved.
FAU - Wijayatunge, Ranjula
AU  - Wijayatunge R
AD  - Dept. of Neurobiology, Duke University Medical Center, Durham, NC 27710, United 
      States.
FAU - Liu, Fang
AU  - Liu F
AD  - Dept. of Neurobiology, Duke University Medical Center, Durham, NC 27710, United 
      States.
FAU - Shpargel, Karl B
AU  - Shpargel KB
AD  - Dept. of Genetics and Lineberger Comprehensive Cancer Center, University of North 
      Carolina, Chapel Hill, NC 27599, United States.
FAU - Wayne, Nicole J
AU  - Wayne NJ
AD  - Dept. of Neurobiology, Duke University Medical Center, Durham, NC 27710, United 
      States.
FAU - Chan, Urann
AU  - Chan U
AD  - Dept. of Neurobiology, Duke University Medical Center, Durham, NC 27710, United 
      States.
FAU - Boua, Jane-Valeriane
AU  - Boua JV
AD  - Dept. of Neurobiology, Duke University Medical Center, Durham, NC 27710, United 
      States.
FAU - Magnuson, Terry
AU  - Magnuson T
AD  - Dept. of Genetics and Lineberger Comprehensive Cancer Center, University of North 
      Carolina, Chapel Hill, NC 27599, United States.
FAU - West, Anne E
AU  - West AE
AD  - Dept. of Neurobiology, Duke University Medical Center, Durham, NC 27710, United 
      States. Electronic address: west@neuro.duke.edu.
LA  - eng
GR  - R01 DA022202/DA/NIDA NIH HHS/United States
GR  - R01 GM101974/GM/NIGMS NIH HHS/United States
GR  - R01 NS098804/NS/NINDS NIH HHS/United States
GR  - R21 NS084336/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Review
DEP - 20171215
PL  - United States
TA  - Mol Cell Neurosci
JT  - Molecular and cellular neurosciences
JID - 9100095
RN  - 0 (Histones)
RN  - EC 1.14.11.- (Histone Demethylases)
RN  - EC 1.14.11.- (Jumonji Domain-Containing Histone Demethylases)
RN  - EC 1.14.11.- (KDM6B protein, human)
SB  - IM
MH  - Animals
MH  - Cytoplasmic Granules/metabolism
MH  - Gene Expression/genetics
MH  - Histone Demethylases/*genetics
MH  - Histones/*genetics/metabolism
MH  - Humans
MH  - Jumonji Domain-Containing Histone Demethylases/*genetics
MH  - Neurons/*metabolism
PMC - PMC5828961
MID - NIHMS920487
OTO - NOTNLM
OT  - BDNF
OT  - Cerebellum
OT  - Histone Demethylase
OT  - Kdm6b
OT  - Neuronal differentiation
EDAT- 2017/12/20 06:00
MHDA- 2019/01/31 06:00
PMCR- 2019/03/01
CRDT- 2017/12/20 06:00
PHST- 2017/07/11 00:00 [received]
PHST- 2017/10/21 00:00 [revised]
PHST- 2017/11/06 00:00 [accepted]
PHST- 2017/12/20 06:00 [pubmed]
PHST- 2019/01/31 06:00 [medline]
PHST- 2017/12/20 06:00 [entrez]
PHST- 2019/03/01 00:00 [pmc-release]
AID - S1044-7431(17)30243-9 [pii]
AID - 10.1016/j.mcn.2017.11.005 [doi]
PST - ppublish
SO  - Mol Cell Neurosci. 2018 Mar;87:4-17. doi: 10.1016/j.mcn.2017.11.005. Epub 2017 
      Dec 15.