TY - JOUR
T1 - Stage-specific induction of DNA methyltransferases in olfactory receptor neuron development
AU - MacDonald, Jessica L.
AU - Gin, Christopher S.Y.
AU - Roskams, A. Jane
N1 - Funding Information:
We would like to thank Erin Currie for excellent technical assistance and members of the Roskams Lab for experimental insights. Thanks to Dr. Frank Margolis (University of Maryland) for his stellar OMP antibody. We would also like to thank Drs. Jacob Hodgson and Louis Lefebvre for their insightful comments on the manuscript. This work was supported by NSERC studentships (to CG and JM) and CIHR and NIH (NIDCD RO1 Dc-04579) (to JR).
PY - 2005/12/15
Y1 - 2005/12/15
N2 - DNA methylation-dependent gene silencing, mediated by DNA methyltransferases (DNMTs), is essential for normal mammalian development and its dysregulation has been implicated in neurodevelopmental disorders. Despite this, little is known about DNMTs in the developing or mature nervous system. Here, we show that DNMT1, 3a and 3b are expressed at discrete developmental stages in the olfactory neuron lineage, coincident with key shifts in developmental gene expression. DNMT1 is induced in cycling progenitors and is retained in post-mitotic olfactory receptor neurons (ORNs). DNMT3b is restricted to mitotic olfactory progenitors, whereas DNMT3a is expressed only in post-mitotic immature neurons prior to ORN terminal maturation, coincident with histone deacetylase 2 (HDAC2), a key downstream effector of methylation- dependent chromatin condensation. Similar stage-specific expression of DNMT3b and 3a was also found in other developing sensory and CNS neurons. This suggests that progressive lineage restriction regulated by methylation-dependent silencing could be a highly conserved mechanism shared by multiple lineages in the developing nervous system.
AB - DNA methylation-dependent gene silencing, mediated by DNA methyltransferases (DNMTs), is essential for normal mammalian development and its dysregulation has been implicated in neurodevelopmental disorders. Despite this, little is known about DNMTs in the developing or mature nervous system. Here, we show that DNMT1, 3a and 3b are expressed at discrete developmental stages in the olfactory neuron lineage, coincident with key shifts in developmental gene expression. DNMT1 is induced in cycling progenitors and is retained in post-mitotic olfactory receptor neurons (ORNs). DNMT3b is restricted to mitotic olfactory progenitors, whereas DNMT3a is expressed only in post-mitotic immature neurons prior to ORN terminal maturation, coincident with histone deacetylase 2 (HDAC2), a key downstream effector of methylation- dependent chromatin condensation. Similar stage-specific expression of DNMT3b and 3a was also found in other developing sensory and CNS neurons. This suggests that progressive lineage restriction regulated by methylation-dependent silencing could be a highly conserved mechanism shared by multiple lineages in the developing nervous system.
KW - Epigenetics
KW - Lineage restriction
KW - Methyl binding domain proteins
KW - Neuronal differentiation
UR - http://www.scopus.com/inward/record.url?scp=29144513565&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=29144513565&partnerID=8YFLogxK
U2 - 10.1016/j.ydbio.2005.09.048
DO - 10.1016/j.ydbio.2005.09.048
M3 - Article
C2 - 16288735
AN - SCOPUS:29144513565
SN - 0012-1606
VL - 288
SP - 461
EP - 473
JO - Developmental Biology
JF - Developmental Biology
IS - 2
ER -