Arc And Cellular Reactivation

"Immediate early genes" (IEGs) is a term that describes a diverse family of genes that have in common rapid regulation at the transcriptional level. Typically in neurons IEGs respond in an activity-dependent fashion within about 5-15 minutes of cellular stimulation. This rapid transcrip-tional response of a wide variety of genes clearly indicates the presence of signal transduction mechanisms that can quickly carry a signal from the neuronal cell surface to the nucleus.

IEGs code for proteins with a wide variety of cell functions. One major category is transcription factors, and the well-known transcription factors c-fos, c-jun, jun-B, and zif268 are indeed immediate early genes. This category of IEGs indicates that there likely are secondary and tertiary waves of altered transcription in response to increased IEG expression and implies that activity-dependent alterations in neuronal gene expression are indeed likely to be quite complex and subject to elaborate control mechanisms. Along these lines, the term "immediate early gene" arises from early studies of transcriptional regulation in nonneuronal cells, where temporal waves of altered gene expression were observed and termed immediate early, early, and late.

Another category of IEGs code for cytoskeletal and structural proteins like Homer 1A, actin, and Arc (initially discovered as Activity-regulated gene 3.1, or Arg3.1). Work from Paul Worley and his collaborators Ozzie Steward, Carol Barnes,

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