Transcriptional control in myelinating glia: flavors and spices

Transcriptional control in myelinating glia is often described in terms of a handful of trans-acting proteins with preferential expression in these cells. An equally valid approach is the identification of cis-acting elements in genes, which are specifically transcribed in myelinating glia. Regulatory regions of several myelin genes have been analyzed in transgenic animals, transient transfections and in vitro. In some cases, these studies have identified regions responsible for glial expression within the promoters or immediate upstream regions. Other myelin genes possess promoters, which simply secure basal levels of transcription, but do not contain glia-specific cis-acting elements. Promoters of myelin genes also differ strongly in other respects. They either contain a TATA-box or are TATA-less and GC-rich. They exhibit multiple transcription initiation sites or a single strong one. Binding sites for general transcription factors, such as NF-I, Sp1, and CAAT-box binding proteins, and for downstream effectors of major signaling pathways are found in them in abundance. In agreement, members of the AP-1, CREB, STAT, and NF-kappaB families are well-described components of the transcription machinery in myelinating glia. Together with several members of the nuclear receptor family, they are an intrinsic part of the transcriptional control in myelinating glia.