Title

A role for nuclear factor I in the intrinsic control of cerebellar granule neuron gene expression

UMMS Affiliation

University of Massachusetts Medical School Department of Physiology

Publication Date

10-7-2004

Document Type

Article

Subjects

Animals; Base Sequence; Binding, Competitive; Blotting, Western; CCAAT-Enhancer-Binding Proteins; Cell Differentiation; Cell Line; Cell Line, Tumor; Cell Nucleus; Cells, Cultured; Cerebellum; Chromatin; Cytoplasmic Granules; GABA Plasma Membrane Transport Proteins; *Gene Expression Regulation; Humans; Immunohistochemistry; Immunoprecipitation; Lentivirus; Luciferases; Membrane Transport Proteins; Mice; Mice, Knockout; Molecular Sequence Data; NFI Transcription Factors; Neurons; Plasmids; Promoter Regions (Genetics); Receptors, GABA-A; Reverse Transcriptase Polymerase Chain Reaction; Transcription Factors; Transcription, Genetic; Transgenes

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

Nervous system formation requires the elaboration of a complex series of differentiation events in both a spatially and maturation-regulated manner. A fundamental question is how neuronal subtype specification and developmental gene expression are controlled within maturing neurons. The alpha6 subunit of the gamma-aminobutyric acid type A (GABA(A)) receptor (GABRA6) is preferentially expressed in cerebellar granule neurons and is part of an intrinsic program directing their differentiation. We have employed a lentiviral approach to examine the transcriptional mechanisms controlling neuronal subtype-selective expression of this gene. These studies demonstrated that nuclear factor I (NFI) proteins are required for both transgenic GABRA6 promoter activity as well as endogenous expression of this gene in cerebellar granule neurons. Chromatin immunoprecipitation also showed that NFI proteins are bound to the GABRA6 promoter in these cells in vivo. Furthermore, analyses of gene knockout mice revealed that Nfia is specifically required for normal expression of the GABRA6 gene in cerebellar granule neurons. NFI expression and DNA binding activity are highly enriched in granule neurons, implicating this transcription factor family in the neuronal subtype-selective expression of the GABRA6 gene. These studies define a new role for NFI proteins as neuronal subtype-enriched transcriptional regulators that participate in an intrinsic transcriptional program directing the differentiation of cerebellar granule neurons.

Rights and Permissions

Citation: J Biol Chem. 2004 Dec 17;279(51):53491-7. Epub 2004 Oct 1. Link to article on publisher's site

Related Resources

Link to Article in PubMed

Journal/Book/Conference Title

The Journal of biological chemistry

PubMed ID

15466411