The S/G2‐specific transcription of the human cdc25C gene is due to the periodic occupation of a repressor element (‘cell cycle‐dependent element’; CDE) located in the region of the basal promoter. Protein binding to the major groove of the CDE in G0 and G1 results in a phase‐specific repression of activated transcription. We now show that CDE‐mediated repression is also the major principle underlying the periodic transcription of the human cyclin A and cdc2 genes. A single point mutation within the CDE results in a 10‐ to 20‐fold deregulation in G0 and an almost complete loss of cell cycle regulation of all three genes. In addition, the cdc25C, cyclin A and cdc2 genes share an identical 5 bp region (‘cell cycle genes homology region’; CHR) starting at an identical position, six nucleotides 3′ to the CDE. Strikingly, mutation of the CHR region in each of the three promoters produces the same phenotype as the mutation of the CDE, i.e. a dramatic deregulation in G0. In agreement with these results, in vivo DMS footprinting showed the periodic occupation of the cyclin A CDE in the major groove, and of the CHR in the minor groove. Finally, all three genes bear conspicuous similarities in their upstream activating sequences (UAS). This applies in particular to the presence of NF‐Y and Sp1 binding sites which, in the cdc25C gene, have been shown to be the targets of repression through the CDE.(ABSTRACT TRUNCATED AT 250 WORDS)
In the contemporary conditions of neoliberal governmentality, and the emerging ‘gig economy,’ standard employment relationships appear to be giving way to precarious work. This article examines the mechanisms of biopower and techniques of managerial control that underpin—and produce consent for—precarious work and nonstandard work arrangements. Based on an ethnographic study, the article shows how a globally operating direct sales organization deploys particular techniques of government to mobilize and manage its precarious workers as a network of enterprise-units: as a community of active and productive economic agents who willingly reconstitute themselves and their lives as enterprises to pursue self-efficacy, autonomy and self-worth as individuals. The article contributes to the literature on organizational power, particularly Foucauldian studies of the workplace, in three ways: (1) by building a theoretical analytics of government perspective on managerial control that highlights the nondisciplinary, biopolitical forms of power that underpin employment relations under the conditions of neoliberal governmentality; (2) by extending the theory of enterprise culture to the domain of precarious work to examine the mechanisms of biopower that underpin ongoing transformations in the sphere of work; and (3) by shifting critical attention to the lived experience of precarious workers in practice.
The late S/G2-specific transcription of the human cdc25C gene is dependent on an initiator-proximal repressor element (CDE) and an upstream activating sequence (UAS) of undefined nature. We now show that these upstream sequences harbour multiple in vivo protein binding sites that interact with transcriptional activators and form separable, context-independent functional modules. Major components of the UAS are a bona fide Sp1 site and three direct sequence repeats (Yc-boxes). The Yc-boxes interact with the CCAAT-box binding protein NF-Y and are critically dependent on synergistic interactions for efficient transcription activation. The NF-Y complexes, as well as Sp1, are constitutive activators, whose activation function is periodically repressed through the CDE. These observations indicate that the cell cycle regulation of cdc25C transcription is mainly due to the CDE-mediated repression of glutamine-rich activators.
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