Nuclear Organization and Myt1 Interaction in Transcriptional Control of Neural Cell Differentiation
Abstract
Neural cell differentiation is a complex set of events beginning with cells responding to both soluble and cell contact-dependent external signals. These signals activate pathways that lead to changes in gene expression patterns, which ultimately give rise to the differentiated cell phenotype. In these studies, potential mechanisms regulating different aspects of oligodendrocyte differentiation were explored. Specifically, these studies examined the contribution of gene and protein localization to the establishment and/or maintenance of terminally differentiated oligodendrocyte gene expression patterns and the role of myelin transcription factor 1 (Myt1) in the regulation of oligodendrocyte proliferation and differentiation. Myt1 is a zinc-finger DNA-binding protein that is expressed in neural progenitors and is localized to discrete domains within the nucleus of oligodendrocyte progenitors. Primary oligodendrocyte lineage cells were examined during cell differentiation in order to study the localization of the highly expressed tissue-specific proteolipid protein gene relative to nuclear proteins such as Myt1 and splicing factors within interphase nuclei. These data support a nuclear organization model in which nuclear proteins and genes exhibit specific patterns of distribution within nuclei, and activation of tissue-specific genes is associated with changes in protein distribution rather than changes in gene localization. Myt1 contains six zinc-finger DNA-binding domains with sets of two N-terminal and of four C-terminal zinc-fingers. A retroviral expression system was used to overexpress the four zinc-finger DNA-binding domain of Myt1 (4FMyt1) which lacks the putative domains for protein-protein interaction and transcriptional activation. In a dominant negative study, expression of 4FMyt1 inhibited both proliferation and differentiation of oligodendrocyte
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2002
- Accession Number
- ADA421549
Entities
People
- Joseph A. Nielsen
Organizations
- Uniformed Services University of the Health Sciences