An improved understanding of nuclear architecture has begun to reveal how genome organization affects transcription and other biological functions. Changes in chromatin conformation and composition influence gene expression [1]. These epigenetically heritable alterations are one of the ways in which cells respond to, and remember, developmental or environmental stimuli. Epigenetic regulation and memory involve mitotically — and sometimes trans-generationally — heritable mechanisms [2]. For example, in worms, fruit flies, mice, and humans, changes in paternal or maternal diet can reprogram the metabolism of offspring in future generations to cause a predisposition toward obesity or associated conditions 3, 4, 5, 6••, 7. Stable changes in transcription are associated with changes in DNA methylation, posttranslational histone modifications [8], transcription factor (TF) activity, noncoding RNA expression, or mRNA stability [9]. Recent experiences can also be remembered for several mitotic cell divisions; some inducible genes exhibit heritable epigenetic transcriptional memory following exposure to a transient stimulus [10]. Transcriptional memory poises genes for faster reactivation, allowing cells to better adapt to a previously encountered condition 11, 12, 13, 14••, 15. Stable transcriptional states and less-stable transcriptional memory both involve heritable regulation of promoter and enhancer functions in cis. In this review, we will discuss both general molecular mechanisms of heritable epigenetic regulation and, more specifically, epigenetic transcriptional memory.