AbstractThe production of myelin by oligodendrocytes requires the coordinated, massive synthesis of myelin components, a program that is dependent on transcriptional controls. Myelin transcription factor I (MyTI) was named for its ability to recognize the proteolipid protein (PLP) gene, the most abundantly transcribed central nervous system myelin gene (Kim and Hudson: Mol. Cell Biol. 12:5632, 1992). MyTI is a zinc‐dependent, DNA‐binding protein of the Cys2‐His‐Cys class. The pattern of MyTI expression, documented in the present study, suggests that MyTI may be instrumental in early stages of oligodendrocytic development and myelin production. MyTI mRNA transcripts are more highly expressed in oligodendrocyte progenitors than in differentiated oligodendrocytes. In vitro and in vivo analyses show that MyTI immunoreactivity is stronger in oligodendrocytic progenitors than in mature oligodendrocytes which have already accumulated PLP. In oligodendrocyte progenitors, MyTI immunoreactivity appears as speckles within the nucleus, suggestive of an association of MyTI with a function that is spatially segregated into discrete nuclear domains. MyTI continues to be expressed in cells transcribing PLP. However, as oligodendrocytes accumulate PLP, MyTI immunoreactivity becomes restricted to the cytoplasm and progressively diminishes. Since MyTI has two widely separated sets of DNA‐binding domains and initial MyTI expression markedly precedes PLP expression, we hypothesize the following model: MyTI may play a role in assembling transcriptionally active complexes of PLP, perhaps by bending the DNA of the promoter region to induce an appropriate conformation to enable subsequent binding the DNA of the promoter region to induce an appropriate conformation to enable subsequent binding of additional regulatory proteins. © 1995 Wiley‐Liss, Inc.