The generation of distinct cell types during development depends on the competence of progenitor populations to differentiate along specific lineages. Here we investigate the mechanisms that regulate competence of rodent cortical progenitors to differentiate into astrocytes in response to ciliary neurotrophic factor (CNTF). We found that fibroblast growth factor 2 (FGF2), which by itself does not induce astrocyte-specific gene expression, regulates the ability of CNTF to induce expression of glial fibrillary acidic protein (GFAP). FGF2 facilitates access of the STAT/CBP (signal transducer and activator of transcription/CRE binding protein) complex to the GFAP promoter by inducing Lys4 methylation and suppressing Lys9 methylation of histone H3 at the STAT binding site. Histone methylation at this site is specific to the cell's state of differentiation. In progenitors, the promoter is bound by Lys9-methylated histones, and in astrocytes, it is bound by Lys4-methylated histones, indicating that astrocyte differentiation in vivo involves this switch in chromatin state. Our observations indicate that extracellular signals can regulate access of transcription factors to genomic promoters by local chromatin modification, and thereby regulate developmental competence.

Optogenetic tools use colored light to rapidly control gene expression in space and time. We designed a genetically encoded system that gives Escherichia coli the ability to distinguish between red, green, and blue (RGB) light and respond by changing gene expression. We use this system to produce 'color photographs' on bacterial culture plates by controlling pigment production and to redirect metabolic flux by expressing CRISPRi guide RNAs.

We have examined expression of the genes on Salmonella pathogenicity island 1 (SPI1) during growth under the physiologically well defined standard growth condition of Luria-Bertani medium with aeration. We found that the central regulator hilA and the genes under its control are expressed at the onset of stationary phase. Interestingly, the two-component regulatory genes hilC/ hilD, sirA/barA, and ompR, which are known to modulate expression from the hilA promoter (hilAp) under so-called "inducing conditions" (Luria-Bertani medium containing 0.3 M NaCl without aeration), acted under standard conditions at the stationary phase induction level. The induction of hilAp depended not on RpoS, the stationary phase sigma factor, but on the stringent signal molecule ppGpp. In the ppGpp null mutant background, hilAp showed absolutely no activity. The stationary phase induction of hilAp required spoT but not relA. Consistent with this requirement, hilAp was also induced by carbon source deprivation, which is known to transiently elevate ppGpp mediated by spoT function. The observation that amino acid starvation elicited by the addition of serine hydroxamate did not induce hilAp in a RelA ؉ SpoT ؉ strain suggested that, in addition to ppGpp, some other alteration accompanying entry into the stationary phase might be necessary for induction. It is speculated that during the course of infection Salmonella encounters various stressful environments that are sensed and translated to the intracellular signal, ppGpp, which allows expression of Salmonella virulence genes, including SPI1 genes.

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