Premium
Methyl‐CpG binding proteins are involved in restricting differentiation plasticity in neurons
Author(s) -
Setoguchi Hiroki,
Namihira Masakazu,
Kohyama Jun,
Asano Hirotsugu,
Sanosaka Tsukasa,
Nakashima Kinichi
Publication year - 2006
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.21001
Subject(s) - biology , neuroepithelial cell , neurogenesis , dna methylation , microbiology and biotechnology , mecp2 , glial fibrillary acidic protein , astrocyte , cellular differentiation , neural stem cell , gene expression , gene , genetics , stem cell , neuroscience , central nervous system , immunology , immunohistochemistry , phenotype
Neurons and astrocytes are generated from common neural precursors, yet neurogenesis precedes astrocytogenesis, which normally commences at later stages of development. We have previously reported that a particular cytosine residue within a STAT3‐binding site in the astrocyte‐specific marker glial fibrillary acidic protein (GFAP) gene promoter becomes demethylated in neuroepithelial cells as gestation proceeds. This demethylation correlates tightly with the onset of astrocyte differentiation, suggesting that a change in DNA methylation at cell‐type‐specific gene promoters controls the switch from neurogenesis to astrocytogenesis in the developing brain. Here, we show that late‐gestation neuroepithelial cells, which have already lost the methylation in the STAT3‐binding site within the GFAP promoter, can still give rise to neurons and that these neurons do not respond to a STAT3‐activating cytokine to express GFAP. Members of a transcriptional repressor family, the methylated‐CpG binding proteins (MBDs), including MeCP2, are predominantly expressed in neurons, and ectopic MeCP2 expression inhibited astrocyte differentiation of neuroepithelial cells. Moreover, we found that exon 1 of the GFAP gene remains hypermethylated even in neuroepithelial cells at a late developmental stage and in neurons differentiated from such neuroepithelial cells. We further demonstrate that MeCP2 actually binds to the highly methylated exon 1 of the GFAP gene in neurons. These results suggest that region‐specific DNA methylation and MBDs play an important role in the regulation of differentiation plasticity in neurons. © 2006 Wiley‐Liss, Inc.