Members of this family of DNA binding domains adopt a beta-trefoil fold, that is, a capped beta-barrel with internal pseudo threefold symmetry. In the DNA-binding protein LAG-1, it also is the site of mutually exclusive interactions with NotchIC (and the viral protein EBNA2) and co-repressors (SMRT/N-Cor and CIR) (PUBMED:15297877).
This DNA-binding domain adopts a beta-trefoil fold, that is, a capped beta-barrel with internal pseudo threefold symmetry. In the DNA-binding protein LAG-1, it also is the site of mutually exclusive interactions with NotchIC (and the viral protein EBNA2) and corepressors (SMRT/N-Cor and CIR) [(PUBMED:15297877)].
GO process:
regulation of transcription, DNA-templated (GO:0006355)
GO function:
transcription factor activity, RNA polymerase II proximal promoter sequence-specific DNA binding (GO:0000982), RNA polymerase II proximal promoter sequence-specific DNA binding (GO:0000978)
BACKGROUND: The CSL (CBF1/RBP-Jkappa/Suppressor of Hairless/LAG-1) transcription factor family members are well-known components of the transmembrane receptorNotch signaling pathway, which plays a critical role in metazoan development.They function as context-dependent activators or repressors of transcription oftheir responsive genes, the promoters of which harbor the GTG(G/A)GAA consensuselements. Recently, several studies described Notch-independent activities of theCSL proteins. RESULTS: We have identified putative CSL genes in several fungalspecies, showing that this family is not confined to metazoans. We have analyzed their sequence conservation and identified the presence of well-defined domainstypical of genuine CSL proteins. Furthermore, we have shown that the candidatefungal protein sequences contain highly conserved regions known to be requiredfor sequence-specific DNA binding in their metazoan counterparts. Thephylogenetic analysis of the newly identified fungal CSL proteins revealed theexistence of two distinct classes, both of which are present in all the speciesstudied. CONCLUSION: Our findings support the evolutionary origin of the CSLtranscription factor family in the last common ancestor of fungi and metazoans.We hypothesize that the ancestral CSL function involved DNA binding andNotch-independent regulation of transcription and that this function may still beshared, to a certain degree, by the present CSL family members from both fungiand metazoans.
Crystal structure of the nuclear effector of Notch signaling, CSL, bound to DNA.
EMBO J. 2004; 23: 3441-51
Display abstract
Notch signaling is a conserved pathway of communication between neighboring cellsthat results in cell fate specification, and CSL is the universal transcriptionaleffector of Notch signaling. The Notch intracellular domain translocates to thenucleus after proteolytic release upon Notch extracellular engagement, and there it displaces corepressors from DNA-bound CSL and recruits activators of Notchtarget genes. Here we report the 2.85 A crystal structure of CSL with a targetDNA. CSL comprises three structurally integrated domains: its amino (NTD)- andcarboxy (CTD)-terminal domains are strikingly similar to those of Reltranscription factors, but a surprising beta-trefoil domain (BTD) is insertedbetween them. CSL-bound DNA is recognized specifically by conserved residues fromNTD and BTD. A hydrophobic pocket on BTD is identified as the likely site ofNotch interaction with CSL, which has functional implications for the mechanismof Notch signaling.
