Tissue-specific actions of Pax6 on proliferation-differentiation balance in the developing forebrain are Foxg1-dependent

SummaryDifferences in the growth and maturation of diverse forebrain tissues depends on region-specific transcriptional regulation. Individual transcription factors act simultaneously in multiple regions that develop very differently, raising questions about the extent to which their actions vary regionally. We found that the transcription factor Pax6 affects the transcriptomes and the balance between proliferation and differentiation in opposite directions in murine diencephalon versus cortex. We tested several possible mechanisms to explain Pax6’s tissue-specific actions and found that the presence of the transcription factor Foxg1 in cortex but not diencephalon was most influential. We found that Foxg1 is responsible for many of the differences in cell cycle gene expression between diencephalon and cortex. In cortex lacking Foxg1, Pax6’s action on the balance of proliferation versus differentiation became diencephalon-like. Our findings reveal a mechanism for generating regional forebrain diversity in which the actions of one transcription factor completely reverse the actions of another.

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Temporal Control of Cell Cycle Gene Expression Mediated by E2F Transcription Factors

Cell Cycle ◽

10.4161/cc.4.5.1650 ◽

2005 ◽

Vol 4 (5) ◽

pp. 633-636 ◽

Cited By ~ 13

Author(s):

Wencheng Zhu ◽

Paloma H. Giangrande ◽

Joseph R. Nevins

Keyword(s):

Gene Expression ◽

Cell Cycle ◽

Transcription Factors ◽

Cell Cycle Gene ◽

Temporal Control ◽

E2f Transcription Factors ◽

Cell Cycle Gene Expression

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A toxin-antitoxin system associated transcription factor of Caulobacter crescentus can influence cell cycle-regulated gene expression during the SOS response

10.1101/2020.07.22.216945 ◽

2020 ◽

Author(s):

Koyel Ghosh ◽

Kamilla Ankær Brejndal ◽

Clare L. Kirkpatrick

Keyword(s):

Gene Expression ◽

Cell Cycle ◽

Dna Damage ◽

Transcription Factor ◽

Caulobacter Crescentus ◽

Sos Response ◽

Cell Cycle Gene ◽

Regulated Gene Expression ◽

Cell Cycle Gene Expression

AbstractToxin-antitoxin (TA) systems are widespread in bacterial chromosomes but their functions remain enigmatic. Although many are transcriptionally upregulated by stress conditions, it is unclear what role they play in cellular responses to stress and to what extent the role of a given TA system homologue varies between different bacterial species. In this work we investigate the role of the DNA damage-inducible TA system HigBA of Caulobacter crescentus in the SOS response and discover that in addition to the toxin HigB affecting cell cycle gene expression through inhibition of the master regulator CtrA, HigBA possesses a transcription factor third component, HigC, which both auto-regulates the TA system and acts independently of it. Through HigC, the system exerts downstream effects on antibiotic (ciprofloxacin) resistance and cell cycle gene expression. HigB and HigC had inverse effects on cell cycle gene regulation, with HigB reducing and HigC increasing the expression of CtrA-dependent promoters. Neither HigBA nor HigC had any effect on formation of persister cells in response to ciprofloxacin. Rather, their role in the SOS response appears to be as transcriptional and post-transcriptional regulators of cell cycle-dependent gene expression, transmitting the status of the SOS response as a regulatory input into the cell cycle control network via CtrA.ImportanceAlmost all bacteria respond to DNA damage by upregulating a set of genes that helps them to repair and recover from the damage, known as the SOS response. The set of genes induced during the SOS response varies between species, but frequently includes toxin-antitoxin systems. However, it is unknown what the consequence of inducing these systems is, and whether they provide any benefit to the cells. We show here that the DNA damage-induced TA system HigBA of the asymmetrically dividing bacterium Caulobacter crescentus affects the cell cycle regulation of this bacterium. HigBA also has a transcription factor encoded immediately downstream of it, named here HigC, which controls expression of the TA system and potentially other genes as well. Therefore, this work identifies a new role for TA systems in the DNA damage response, distinct from non-specific stress tolerance mechanisms which had been proposed previously.

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