Premium
Neuronal chromatin dynamics of imprinting in development and disease
Author(s) -
Leung Karen N.,
Chamberlain Stormy J.,
Lalande Marc,
LaSalle Janine M.
Publication year - 2011
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.22958
Subject(s) - epigenetics , chromatin , biology , genomic imprinting , epigenetic regulation of neurogenesis , bivalent chromatin , induced pluripotent stem cell , histone , chromatin remodeling , chromosome conformation capture , epigenomics , genetics , transcription factor , dna methylation , gene , gene expression , embryonic stem cell , enhancer
Epigenetic mechanisms play essential roles in mammalian neurodevelopment and genetic mutations or chromosomal deletions or duplications of epigenetically regulated loci or pathways result in several important human neurodevelopmental disorders. Postnatal mammalian neurons have among the most structured and dynamic nuclear organization of any cell type. Human chromosome 15q11‐13 is an imprinted locus required for normal neurodevelopment and is regulated by a plethora of epigenetic mechanisms in neurons, including multiple noncoding RNAs, parentally imprinted transcription and histone modifications, large‐scale chromatin decondensation, and homologous pairing in mature neurons of the mammalian brain. Here, we describe the multiple epigenetic layers regulating 15q11‐13 gene expression and chromatin dynamics in neurons and propose a model of how noncoding RNAs may influence the unusual neuronal chromatin structure and dynamics at this locus. We also discuss the need for improved neuronal cell culture systems that model human 15q11‐13 and other neurodevelopmental disorders with epigenetic bases in order to test the mechanisms of chromatin dynamics and nuclear organization in neurons. Induced pluripotent stem cells and other stem cell technologies hold promise for improved understanding of and therapeutic interventions for multiple human neurodevelopmental disorders. J. Cell. Biochem. 112: 365–373, 2011. © 2010 Wiley‐Liss, Inc.