Previously formed memories are susceptible to disruption immediately after recall due to a necessity to be reconsolidated after retrieval. Protein translation mechanisms have been widely implicated as being necessary for memory reconsolidation, but gene transcription mechanisms have been much less extensively studied in this context. We found that retrieval of contextual conditioned fear memories activates the NF-κB pathway to regulate histone H3 phosphorylation and acetylation at specific gene promoters in hippocampus, specifically via IKKα and not the NF-κB DNA-binding complex. Behaviorally, we found that inhibition of IKKα regulation of either chromatin structure or NF-κB DNA-binding complex activity leads to impairments in fear memory reconsolidation, and that elevating histone acetylation rescues this memory deficit in the face of IKK blockade. These data provide insights into IKK-regulated transcriptional mechanisms in hippocampus that are necessary for memory reconsolidation. © 2007 Elsevier Inc. All rights reserved.