Gene Ontology annotation through association of InterPro records with GO terms
Automatic assignment of GO terms using logical inference, based on on inter-ontology links
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
Alx1, a member of the Cart1/Alx3/Alx4 subfamily of Paired-class homeodomain proteins, is an essential component of the gene network controlling skeletogenic fate specification in the sea urchin embryo.
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Alx1 was identified as an essential component of the large micromere (skeletogenic) specification network; it is expressed exclusively in the large micromere lineage from the first interphase after these cells are born.
"micromere specification, the homeodomain protein Alx1. Alx1 is expressed ... exclusively by cells of the large micromere lineage beginning in the first"
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Morpholino knockdown shows Alx1 acts early in specification and controls downstream genes required for EMT (ingression) and biomineralization.
"that Alx1 is essential at an early stage of specification and controls ... downstream genes required for epithelial-mesenchymal transition and"
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Alx1 expression is cell autonomous and lies downstream of maternal beta-catenin and Pmar1.
"Expression of Alx1 is cell autonomous and regulated ... maternally through beta-catenin and its downstream effector, Pmar1."
A missing link in the sea urchin embryo gene regulatory network: hesC and the double-negative specification of micromeres.
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alx1 is one of the direct targets of the Pmar1/HesC double-negative gate; HesC knockdown derepresses alx1 throughout the embryo.
"By 12 h after fertilization, the amount of transcript of delta and alx1 had increased 4- to 7-fold above normal in the two experiments performed"
Global regulatory logic for specification of an embryonic cell lineage.
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alx1 is one of the four essential regulatory genes activated by the double-negative gate; loss of function gives a skeleton-minus phenotype and blocks ingression.
"They are four essential regulators of downstream micromere lineage function ... both it and alx1 target genes are required for ingression of the skeletogenic cells"
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Alx1 excludes the alternative non-skeletogenic mesoderm fate by repressing gcm in the micromere lineage.
"a role of the micromere lineage regulator alx1 is to repress gcm in that lineage ... Conversely, if alx1 mRNA is introduced into the egg, gcm expression is dramatically reduced"
Precise cis-regulatory control of spatial and temporal expression of the alx-1 gene in the skeletogenic lineage of s. purpuratus.
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cis-regulatory analysis confirms HesC repression of alx1 and shows that Alx1 protein is a direct auto-activator of its own gene, and an auto-repressor at high concentration (attributed to dimerization).
"we demonstrate that Alx1 protein is both an immediate, direct, auto-activator, and at higher concentrations an auto-repressor"
Genome-wide analysis of the skeletogenic gene regulatory network of sea urchins.
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Genome-wide RNA-seq identified functional targets of Alx1 among PMC effector genes.
"functional targets of Ets1 and Alx1, two ... pivotal, early transcription factors in the PMC GRN"
Functional divergence of paralogous transcription factors supported the evolution of biomineralization in echinoderms.
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Structure-function rescue assay defines the D2 domain as essential for skeletogenic function; Alx4 is not interchangeable with Alx1 unless D2 is inserted.
"Perturbation of alx1 function using antisense morpholinos (MOs) blocks PMC specification while misexpression of alx1 results in the ectopic activation of the skeletogenic program in non-PMC lineages"
Genome-wide identification of binding sites and gene targets of Alx1, a pivotal regulator of echinoderm skeletogenesis.
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ChIP-seq identified Alx1 binding sites genome-wide; many terminal differentiation genes and the intermediate PMC transcription factors receive direct Alx1 inputs, and a conserved palindromic Alx1 site is essential for a representative CRM.
"we used genome-wide ChIP-seq to identify ... Alx1-binding sites and direct gene targets. Our analysis revealed that many ... terminal differentiation genes receive direct transcriptional inputs from Alx1."
Analysis of the DNA-binding properties of Alx1, an evolutionarily conserved regulator of skeletogenesis in echinoderms.
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Purified Alx1 binds directly (EMSA) to TAAT half sites in the Sp-mtmmpb CRM and forms dimeric complexes on them; two half sites are essential for PMC-specific CRM activity, and Alx1 positively regulates most biomineralization genes.
"we show that Alx1 binds directly to several half sites. Moreover, Alx1 forms dimeric complexes at these sites"
Lessons from a transcription factor: Alx1 provides insights into gene regulatory networks, cellular reprogramming, and cell type evolution.
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Review summarizing Alx1 as a core component of the skeletogenic GRN and a key regulator of skeletal cell identity across echinoderms.
"The homeodomain-containing transcription factor, Alx1, was originally ... shown to be a core component of the skeletogenic GRN of the sea urchin embryo."