id: Q9V4C9 gene_symbol: dati product_type: PROTEIN status: COMPLETE taxon: id: NCBITaxon:7227 label: Drosophila melanogaster description: Datilografo (dati, CG2052) is a nuclear Krueppel-like C2H2 zinc-finger protein of Drosophila, carrying an array of six C2H2 fingers in the middle of a long, largely disordered polypeptide. Its fingers are most similar to those of the fly neuronal regulators Squeeze and Rotund and to vertebrate ZNF384, but true dati orthologs are restricted to arthropods. DATI is expressed in neuronal nuclei of the embryonic, larval and adult central nervous system. It is required for the correct number, distribution and projections of cholinergic neurons in the antennal lobe and lateral horn, and in both neuronal precursors and postmitotic neurons. Through a small set of cholinergic neurons it supports female acceptance of male courtship; separately it supports adult locomotion and normal mushroom-body gamma-lobe morphology. It is presumed to act as a sequence-specific transcription factor, but its DNA-binding motif, direct target genes and whether it activates or represses transcription have not been determined. existing_annotations: - term: id: GO:0005634 label: nucleus evidence_type: IEA original_reference_id: GO_REF:0000120 qualifier: located_in supporting_entities: - ARBA:ARBA00026330 - UniProtKB-SubCell:SL-0191 review: action: ACCEPT summary: Nucleus is correct and is supported by gene-specific immunostaining, independent of the ARBA/SubCell electronic inference. reason: Anti-DATI staining in adult brain colocalises with a nuclear mCherry.NLS reporter driven in cholinergic neurons, giving direct evidence for nuclear localization. This matches a multi-finger C2H2 transcription regulator. The ARBA rule behind the IEA row is not used as support. supported_by: - reference_id: PMID:25291190 supporting_text: DATI protein stained in magenta, Cha-Gal4 UAS-mCherry.NLS in green, and the overlap between the two in light magenta or white - term: id: GO:0008344 label: adult locomotory behavior evidence_type: IMP original_reference_id: PMID:25291190 qualifier: involved_in review: action: KEEP_AS_NON_CORE summary: Adult locomotory behavior is a genuine IMP phenotype of dati mutants and RNAi, separable from the receptivity phenotype. reason: Mutant females have a climbing deficit that maps to different neurons from those needed for courtship acceptance. The term records an organism-level behavioral consequence of dati loss in the nervous system and is as precise as the evidence allows. It is not a direct output of the DATI molecular activity, so it is kept as non-core. supported_by: - reference_id: PMID:25291190 supporting_text: Courtship acceptance and locomotor deficits in dati mutant females are separable phenotypes. - term: id: GO:0016319 label: mushroom body development evidence_type: IMP original_reference_id: PMID:25291190 qualifier: involved_in review: action: KEEP_AS_NON_CORE summary: dati mutants have malformed mushroom-body gamma lobes; the phenotype is real but peripheral. reason: The gamma lobes of dati1 homozygotes are withered with altered curvature. The same study shows that knockdown in cholinergic neurons does not reproduce the gamma-lobe defect and that this defect does not explain the receptivity phenotype. It is a developmental requirement outside the main antennal-lobe/lateral-horn circuit, so it is kept as non-core. supported_by: - reference_id: PMID:25291190 supporting_text: the gamma lobes are malformed with a generally withered appearance - reference_id: PMID:25291190 supporting_text: although the loss of dati disrupts the gamma lobe neuropile, the focus of dati-mediated courtship acceptance lies elsewhere in the brain. - term: id: GO:0031175 label: neuron projection development evidence_type: IMP original_reference_id: PMID:25291190 qualifier: involved_in review: action: ACCEPT summary: dati loss disrupts antennal-lobe innervation and cholinergic projections to the lateral horn; this is a core developmental output of the neuronal regulator. reason: Mutant antennal-lobe neuropile is reduced, indicating defective innervation, and cholinergic projections from the antennal lobe to the lateral horn are affected. Together with the precursor and postmitotic requirements, this supports a role in building the projections of the neurons that express DATI. The process is cell-autonomous to the dati-expressing neurons, not a remote organismal phenotype. supported_by: - reference_id: PMID:25291190 supporting_text: the cholinergic projections from the antennal lobe towards the lateral horn are also affected - reference_id: PMID:25291190 supporting_text: Note that the antennal lobe neuropile in (E) is smaller than in (B), which indicates defects in innervation. - term: id: GO:0045925 label: positive regulation of female receptivity evidence_type: IMP original_reference_id: PMID:25291190 qualifier: involved_in review: action: KEEP_AS_NON_CORE summary: dati is required in a small set of cholinergic neurons for female courtship acceptance; this is a well-supported behavioral consequence of dati loss. reason: Rejection is reverted by precise excision, reproduced by pan-neuronal and cholinergic RNAi, and separable from the locomotor defect. Positive regulation of female receptivity is the correct term for the phenotype. DATI acts by shaping the neurons that mediate the behavior, not as a regulator of the behavior itself, so the term is kept as non-core. supported_by: - reference_id: PMID:25291190 supporting_text: Expression of dati-RNAi specifically in cholinergic neurons causes the female rejection behavior. - reference_id: PMID:25291190 supporting_text: Courtship acceptance and locomotor deficits in dati mutant females are separable phenotypes. - term: id: GO:0048699 label: generation of neurons evidence_type: IMP original_reference_id: PMID:25291190 qualifier: involved_in review: action: ACCEPT summary: dati is required in neuronal precursors and postmitotic neurons for the correct number and distribution of cholinergic neurons. reason: dati1 homozygotes lose cholinergic projection neurons in the antennal lobe and have extra, enlarged CHA-positive cells near the lateral horn. The authors conclude that dati is needed in precursors as well as postmitotic neurons. They also state that dati does not determine cholinergic identity as such, so generation of neurons is preferred over a fate-commitment term. This is consistent with its expression late in the embryonic neuroblast transcription-factor cascade. supported_by: - reference_id: PMID:25291190 supporting_text: Homozygosity for dati1 causes loss of cholinergic projection neurons in the antennal lobe. - reference_id: PMID:25291190 supporting_text: Together, these results show that dati is required in postmitotic neurons as well as in the precursors of these cells. - reference_id: PMID:25291190 supporting_text: these experiments revealed that dati is not required to determine cholinergic cell identity. - term: id: GO:0003700 label: DNA-binding transcription factor activity evidence_type: ISS original_reference_id: PMID:25291190 review: action: NEW summary: DATI is a nuclear six-finger C2H2 protein classified as a Krueppel-like transcription factor; DNA-binding transcription factor activity is inferred from domain architecture. reason: The protein carries six C2H2 zinc fingers detected by PROSITE/Pfam/InterPro, the fingers are intact in every annotated isoform, and DATI is nuclear in neurons. The primary study classifies it as a Krueppel-like zinc-finger transcription factor. No DNA-binding or reporter assay exists for DATI itself, and its relatives (Squeeze, Rotund, ZNF384) are paralogs or distant homologs in different PANTHER subfamilies or families. The general term is therefore proposed, without RNA polymerase II specificity, a binding motif, or an activator/repressor direction. Nmp4/ZNF384 finger-mapping data are not transferred. supported_by: - reference_id: PMID:25291190 supporting_text: dati encodes a zinc finger transcription factor closely related to rotund (rn) and squeeze (sqz) with homologs in several species, including humans - reference_id: file:DROME/dati/dati-uniprot.txt record_section: ["DR:InterPro"] supporting_text: DR InterPro; IPR013087; Znf_C2H2_type. - reference_id: file:DROME/dati/dati-uniprot.txt record_section: ["DR:PROSITE"] supporting_text: DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 6. - reference_id: file:DROME/dati/dati-bioinformatics/RESULTS-rereview.md supporting_text: All six C2H2 motifs and the flanking sequence are otherwise identical, so Q9V4C9 is a full-length product of the gene and not a fragment. - reference_id: file:DROME/dati/dati-deep-research-falcon.md supporting_text: Its exact DNA-binding motif, direct target genes, transcriptional polarity, cofactors, and isoform-specific functions remain unknown. references: - id: GO_REF:0000120 title: Combined Automated Annotation using Multiple IEA Methods findings: [] - id: PMID:25291190 title: The KRÜPPEL-like transcription factor DATILÓGRAFO is required in specific cholinergic neurons for sexual receptivity in Drosophila females. findings: [] full_text_unavailable: false reference_review: relevance: HIGH correctness: VERIFIED review_notes: Full text cached (PMC4188565). The only primary study of dati; source of all FlyBase IMP rows and the nuclear immunostaining. - id: PMID:11867614 title: DNA binding and gene activation properties of the Nmp4 nuclear matrix transcription factors. full_text_unavailable: true findings: [] reference_review: relevance: LOW correctness: MISCITED review_notes: Correct Nmp4/ZNF384 paper, but it was used in the first-pass review as support for DATI DNA binding. ZNF384 is in a different PANTHER family (PTHR23234) from dati (PTHR16515), and the dati primary paper restricts true dati orthologs to arthropods. No longer used as support; retained for provenance. - id: file:DROME/dati/dati-bioinformatics/RESULTS-rereview.md title: 'dati re-review: isoform comparison and zinc-finger-array relatives' findings: [] - id: file:DROME/dati/dati-deep-research-falcon.md title: Falcon deep research report for dati findings: [] - id: file:DROME/dati/dati-uniprot.txt title: UniProt record Q9V4C9 (dati isoform B) findings: [] core_functions: - description: Nuclear C2H2 zinc-finger transcription regulator acting in neuronal precursors and postmitotic neurons to build the cholinergic antennal-lobe and lateral-horn neurons and their projections. DNA-binding transcription factor activity is inferred from the six-finger architecture; no motif or target has been shown. molecular_function: id: GO:0003700 label: DNA-binding transcription factor activity directly_involved_in: - id: GO:0048699 label: generation of neurons - id: GO:0031175 label: neuron projection development locations: - id: GO:0005634 label: nucleus supported_by: - reference_id: PMID:25291190 supporting_text: Here we described DATI, a zinc finger transcription factor related to the Drosophila Rotund and Squeeze and the vertebrate ZNF384 - reference_id: PMID:25291190 supporting_text: Together, these results show that dati is required in postmitotic neurons as well as in the precursors of these cells. - reference_id: PMID:25291190 supporting_text: DATI protein stained in magenta, Cha-Gal4 UAS-mCherry.NLS in green, and the overlap between the two in light magenta or white - reference_id: file:DROME/dati/dati-uniprot.txt record_section: ["DR:PROSITE"] supporting_text: DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 6. suggested_questions: - question: Which DNA sequence do the six DATI zinc fingers recognise, and does DATI activate or repress its targets in cholinergic neurons? - question: Do the isoform B and A/C forms, which differ by a 10-residue insertion in finger 4, have different DNA-binding specificity? - question: Is PANTHER placement of dati products in PTHR16515:SF49 (isoforms A-C), SF66 (GH06573p, with Squeeze) and PTHR24393 (isoform D) a classification artefact, given the identical finger arrays? suggested_experiments: - description: Determine the DATI binding motif by SELEX or protein-binding microarray of the finger array (isoforms B and A/C), then profile occupancy in brain neurons by targeted DamID or CUT&RUN. - description: Profile transcriptomes of dati-RNAi versus control Cha-Gal4 neurons, and test candidate targets in reporter assays to establish activator or repressor function.