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Towards resolving the transcription factor network controlling myelin gene expression.

Debra Fulton 1, 2, 3, 4 Eric Denarier 5 Hana Friedman 2, 3, 4 Wyeth Wasserman 1 Alan Peterson 2, 3, 4, *
* Corresponding author
5 ANTE-INSERM U836, équipe 1, Physiopathologie du cytosquelette
Department of Neurology and Neurosurgery, Department of Human Genetics [Montréal], Department of Oncology [Montréal]
Abstract : In the central nervous system (CNS), myelin is produced from spirally-wrapped oligodendrocyte plasma membrane and, as exemplified by the debilitating effects of inherited or acquired myelin abnormalities in diseases such as multiple sclerosis, it plays a critical role in nervous system function. Myelin sheath production coincides with rapid up-regulation of numerous genes. The complexity of their subsequent expression patterns, along with recently recognized heterogeneity within the oligodendrocyte lineage, suggest that the regulatory networks controlling such genes drive multiple context-specific transcriptional programs. Conferring this nuanced level of control likely involves a large repertoire of interacting transcription factors (TFs). Here, we combined novel strategies of computational sequence analyses with in vivo functional analysis to establish a TF network model of coordinate myelin-associated gene transcription. Notably, the network model captures regulatory DNA elements and TFs known to regulate oligodendrocyte myelin gene transcription and/or oligodendrocyte development, thereby validating our approach. Further, it links to numerous TFs with previously unsuspected roles in CNS myelination and suggests collaborative relationships amongst both known and novel TFs, thus providing deeper insight into the myelin gene transcriptional network.
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Debra Fulton, Eric Denarier, Hana Friedman, Wyeth Wasserman, Alan Peterson. Towards resolving the transcription factor network controlling myelin gene expression.. Nucleic Acids Research, Oxford University Press, 2011, 39 (18), pp.7974-91. ⟨10.1093/nar/gkr326⟩. ⟨inserm-00638447⟩

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