Abstract
The C-module-binding factor (CbfA) is a multidomain protein that belongs to the family of jumonji-type (JmjC) transcription regulators. In the social amoeba Dictyostelium discoideum, CbfA regulates gene expression during the unicellular growth phase and multicellular development. CbfA and a related D. discoideum CbfA-like protein, CbfB, share a paralogous domain arrangement that includes the JmjC domain, presumably a chromatin-remodeling activity, and two zinc finger-like (ZF) motifs. On the other hand, the CbfA and CbfB proteins have completely different carboxy-terminal domains, suggesting that the plasticity of such domains may have contributed to the adaptation of the CbfA-like transcription factors to the rapid genome evolution in the dictyostelid clade. To support this hypothesis we performed DNA microarray and real-time RT-PCR measurements and found that CbfA regulates at least 160 genes during the vegetative growth of D. discoideum cells. Functional annotation of these genes revealed that CbfA predominantly controls the expression of gene products involved in housekeeping functions, such as carbohydrate, purine nucleoside/nucleotide, and amino acid metabolism. The CbfA protein displays two different mechanisms of gene regulation. The expression of one set of CbfA-dependent genes requires at least the JmjC/ZF domain of the CbfA protein and thus may depend on chromatin modulation. Regulation of the larger group of genes, however, does not depend on the entire CbfA protein and requires only the carboxy-terminal domain of CbfA (CbfA-CTD). An AT-hook motif located in CbfA-CTD, which is known to mediate DNA binding to A+T-rich sequences in vitro, contributed to CbfA-CTD-dependent gene regulatory functions in vivo.
Highlights
Dictyostelium discoideum is a unicellular, amoeboid organism that lives in the soil and feeds on bacteria
We found that full-length C-module-binding factor (CbfA) has both transcription activating and repressing activities, and that the factor regulates more than 160 genes of the D. discoideum genome
We cannot discriminate yet whether regulation of these genes requires the CbfA-carboxy-terminal domain (CTD), we assume that this activity of CbfA involves chromatin remodeling catalyzed by the CbfA-JmjC domain
Summary
Dictyostelium discoideum is a unicellular, amoeboid organism that lives in the soil and feeds on bacteria. Cyclic AMP (cAMP) coordinates both the aggregation and multicellular development of D. discoideum; it acts as a chemoattractant and as a morphogen. Aggregation-competent D. discoideum cells sense cAMP by means of the cAMP-specific, G protein-coupled receptors CAR1–3 [2]. Signaling by CAR1 during aggregation leads to the activation of effector enzymes such as adenylyl cyclase (ACA) and extracellular signal-related kinase 2 (ERK2) by both G protein-dependent and independent mechanisms. Protein kinase A, activated by elevated intracellular cAMP levels, phosphorylates downstream substrates and mediates the induction of genes required for aggregation and post-aggregation development. Since the gene products required for the production and sensing of cAMP are themselves induced by cAMP, a positive feedback loop is established that is required for the full induction of genes that regulate multicellular development [2]
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