SUMMARYIt is widely accepted that morphogenetic gradients determine cell identity by concentration-dependent activation of target genes. How precise is each step in the gene expression process that acts downstream of morphogens, however, remains unclear. The Bicoid morphogen is a transcription factor directly activating its target genes and provides thus a simple system to address this issue in a quantitative manner. Recent studies indicate that the Bicoid gradient is precisely established in Drosophila embryos after eight nuclear divisions (cycle 9) and that target protein expression is specified five divisions later (cycle 14), with a precision that corresponds to a relative difference of Bicoid concentration of 10%. To understand how such precision was achieved, we directly analyzed nascent transcripts of the hunchback target gene at their site of synthesis. Most anterior nuclei in cycle 11 interphasic embryos exhibit efficient biallelic transcription of hunchback and this synchronous expression is specified within a 10% difference of Bicoid concentration. The fast diffusion of Bcd-EGFP (7.7 m 2 /s) that we captured by fluorescent correlation spectroscopy in the nucleus is consistent with this robust expression at cycle 11. However, given the interruption of transcription during mitosis, it remains too slow to be consistent with precise de novo reading of Bicoid concentration at each interphase, suggesting the existence of a memorization process that recalls this information from earlier cycles. The two anterior maternal morphogens, Bicoid and Hunchback, contribute differently to this early response: whereas Bicoid provides dose-dependent positional information along the axis, maternal Hunchback is required for the synchrony of the response and is therefore likely to be involved in this memorization process.

Mammalian dosage compensation involves silencing of one of the two X chromosomes in females and is controlled by the X-inactivation center (Xic). The Xic, which includes Xist and its antisense transcription unit Tsix/Xite, somehow senses the number of X chromosomes and triggers Xist up-regulation from one of the two X chromosomes in females. We found that a segment of the mouse Xic lying several hundred kilobases upstream of Xist brings the two Xics together before the onset of X inactivation. This region can autonomously drive Xic trans-interactions even as an ectopic single-copy transgene. Its introduction into male embryonic stem cells is strongly selected against, consistent with a possible role in trans-activating Xist. We propose that homologous associations driven by this novel X-pairing region (Xpr) of the Xic enable a cell to sense that more than one X chromosome is present and coordinate reciprocal Xist/Tsix expression.