Transcriptional dynamics, denucleation, and gene regulation in embryonic lens development

Summary Transcription of genes occurs in apparently irregular pulses of activity termed transcriptional bursts. In contrast, cellular differentiation is marked by coordinated gene expression of batteries of genes required for cellular specialization. Ocular lens is comprised of two compartments: the lens epithelium and lens fibers. Position of individual cells within the lens is directly related to their differentiation status, marked by expression of individual crystallin genes. Another hallmark of lens fiber cell differentiation is organized degradation of their organelles. It is currently not known how transcription is terminated in the disintegrating lens fiber cell nuclei and what are the external and internal components of this process critical for lens transparency. Onset of expression of different crystallins follows the temporal pattern Cryaa > Crybb1 > Cryga in differentiating lens fibers. Surprisingly, expression of Cryaa is terminated in “normal” fiber cell nuclei while expression of Cryga persists even in highly condensed nuclei just about to be disintegrated. Differentiation influences both transcriptional burst size and frequency as well as spatial pairing of different chromosomes that carry crystallin genes.