CbfA, the C-module DNA-binding factor, plays an essential role in the initiation of Dictyostelium discoideum development.

CbfA, the C-module DNA-binding factor, plays an essential role in the initiation of Dictyostelium discoideum development.
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CbfA,C 模块 DNA 结合因子,在盘基网柄菌发育的启动中起着重要作用。

DOI:
10.1128/ec.3.5.1349-1358.2004
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发表时间:
2004
期刊:
Eukaryotic cell.
影响因子:
--
通讯作者:
Dingermann,Theodor
Dingermann,Theodor
中科院分区:
--
文献类型:
--
作者:
Winckler,Thomas;Iranfar,Negin;Beck,Peter;Jennes,Ingo;Siol,Oliver;Baik,Unha;Loomis,WilliamF;Dingermann,Theodor

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We recently isolated fromDictyostelium discoideumcells a DNA-binding protein, CbfA, that interacts in vitro with a regulatory element in retrotransposon TRE5-A. We have generated a mutant strain that expresses CbfA at <5% of the wild-type level to characterize the consequences forD. discoideumcell physiology. We found that the multicellular development program leading to fruiting body formation is highly compromised in the mutant. The cells cannot aggregate and stay as a monolayer almost indefinitely. The cells respond properly to prestarvation conditions by expressing discoidin in a cell density-dependent manner. A genomewide microarray-assisted expression analysis combined with Northern blot analyses revealed a failure of CbfA-depleted cells to induce the gene encoding aggregation-specific adenylyl cyclase ACA and other genes required for cyclic AMP (cAMP) signal relay, which is necessary for aggregation and subsequent multicellular development. However, thecbfAmutant aggregated efficiently when mixed with as few as 5% wild-type cells. Moreover, pulsingcbfAmutant cells developing in suspension with nanomolar levels of cAMP resulted in induction ofacaAand other early developmental genes. Although the response was less efficient and slower than in wild-type cells, it showed that cells depleted of CbfA are able to initiate development if given exogenous cAMP signals. Ectopic expression of the gene encoding the catalytic subunit of protein kinase A restored multicellular development of the mutant. We conclude that sensing of cell density and starvation are independent of CbfA, whereas CbfA is essential for the pattern of gene expression which establishes the genetic network leading to aggregation and multicellular development ofD. discoideum.