Regulatory machinery is focally organized in the interphase nucleus. The information contained in these focal nuclear microenvironments must be inherited during cell division to sustain physiologically responsive gene expression in progeny cells. Recent results suggest that focal mitotic retention of phenotypic transcription factors at promoters together with histone modifications and DNA methylation — a mechanism collectively known as gene bookmarking — is a novel parameter of inherited epigenetic control that sustains cellular identity after mitosis. The epigenetic signatures imposed by bookmarking poise genes for activation or suppression following mitosis. We discuss the implications of phenotypic transcription factor retention on mitotic chromosomes in biological control and disease.