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    Zrs1 zone of polarising activity regulatory sequence 1 [ Mus musculus (house mouse) ]

    Gene ID: 105804842, updated on 17-Aug-2024

    Summary

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    Official Symbol
    Zrs1provided by MGI
    Official Full Name
    zone of polarising activity regulatory sequence 1provided by MGI
    Primary source
    MGI:MGI:3028525
    Gene type
    biological region
    Feature type(s)
    misc_feature: conserved_region
    protein_bind
    regulatory: enhancer, transcriptional_cis_regulatory_region
    RefSeq status
    REVIEWED
    Organism
    Mus musculus
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
    Also known as
    Zrs; Mfcs1; Zrs/Lmbr1
    Summary
    This locus represents a highly conserved functional element that is located in an intron of the limb development membrane protein 1 gene. In the developing limb bud, this element functions as a long-range enhancer of the sonic hedgehog (Shh) gene, which is located approximately 1 Mb downstream. Multiple transcription factor binding sites have been identified, and long-range looping interactions have been shown between this element and the Shh gene. Mutations in this element disrupt limb patterning in mice. In the orthologous human element, mutations can result in a range of congenital limb malformations, including preaxial polydactyly, triphalangeal thumbs, Werner mesomelic syndrome (WMS) and polysyndactyly. [provided by RefSeq, Feb 2019]
    Orthologs
    human all
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    Genomic context

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    See Zrs1 in Genome Data Viewer
    Location:
    5; 5
    Annotation release Status Assembly Chr Location
    RS_2024_02 current GRCm39 (GCF_000001635.27) 5 NC_000071.7 (29519495..29520860)
    108.20200622 previous assembly GRCm38.p6 (GCF_000001635.26) 5 NC_000071.6 (29314497..29315862)

    Chromosome 5 - NC_000071.7Genomic Context describing neighboring genes Neighboring gene STARR-seq mESC enhancer starr_12726 Neighboring gene predicted gene, 35881 Neighboring gene mammal reptile conserved sequence 1 Neighboring gene STARR-seq mESC enhancer starr_12727 Neighboring gene STARR-seq mESC enhancer starr_12728 Neighboring gene mammal fish conserved sequence 3 Neighboring gene STARR-seq mESC enhancer starr_12729 Neighboring gene mammal fish conserved sequence 4 Neighboring gene ring finger protein 32 Neighboring gene predicted gene 7420 Neighboring gene mammal amphibian conserved sequence 1 Neighboring gene limb region 1 Neighboring gene STARR-seq mESC enhancer starr_12732 Neighboring gene STARR-seq mESC enhancer starr_12733 Neighboring gene STARR-seq mESC enhancer starr_12734 Neighboring gene STARR-positive B cell enhancer ABC_E9634 Neighboring gene predicted gene, 36086 Neighboring gene STARR-positive B cell enhancer ABC_E9252 Neighboring gene nucleolar protein with MIF4G domain 1

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Bibliography

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    Related articles in PubMed

    1. A point mutation in the pre-ZRS disrupts sonic hedgehog expression in the limb bud and results in triphalangeal thumb-polysyndactyly syndrome. Potuijt JWP, et al. Genet Med, 2018 Nov. PMID 29543231
    2. 3D chromatin regulation of Sonic hedgehog in the limb buds. Ferrai C, et al. Dev Cell, 2009 Jan. PMID 19154714
    3. ZRS 406A>G mutation in patients with tibial hypoplasia, polydactyly and triphalangeal first fingers. Norbnop P, et al. J Hum Genet, 2014 Aug. PMID 24965254
    4. The chicken polydactyly (Po) locus causes allelic imbalance and ectopic expression of Shh during limb development. Dunn IC, et al. Dev Dyn, 2011 May. PMID 21465618
    5. Genetic heterogeneity in type III familial cutaneous syndactyly and linkage to chromosome 7q36. Al-Qattan MM, et al. Am J Med Genet A, 2013 Jul. PMID 23686920

    See all (29) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. we report the first case of triphalangeal thumb-polysyndactyly syndrome (TPT-PS) to be associated with mutations in this region and show via mouse enhancer assays how this mutation leads to ectopic expression throughout the developing limb bud.Our work describes the first mutation in the pZRS to be associated with TPT-PS
      Title: A point mutation in the pre-ZRS disrupts sonic hedgehog expression in the limb bud and results in triphalangeal thumb-polysyndactyly syndrome.
    2. The E26 transformation-specific transcription factor, ETV4, which is induced by fibroblast growth factor signalling and acts as a repressor of ZRS activity, interacts with the histone deacetylase HDAC2 and ensures that the poised ZRS remains transcriptionally inactive.
      Title: Fibroblast growth factors (FGFs) prime the limb specific Shh enhancer for chromatin changes that balance histone acetylation mediated by E26 transformation-specific (ETS) factors.
    3. PPD caused by mutations in MFCS1 has two major types of molecular etiology: loss of a cis-motif for negative regulation of Shh, and acquisition of a new cis-motif binding to a preexisting transcription factor, as represented by the Hx mutation.
      Title: Two Types of Etiological Mutation in the Limb-Specific Enhancer of Shh.
    Submit: New GeneRIF Correction

    General gene information

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    Homology

    Other Names

    • VISTA enhancer mm1189
    • ZPA regulatory sequence
    • ZPA-specific enhancer
    • Zrs limb enhancer
    • Zrs/Shh enhancer
    • mammal-fish-conserved-sequence 1
    • zone of polarizing activity regulatory sequence

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_042170.2 

      Range
      101..1466
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCm39 C57BL/6J

    Genomic

    1. NC_000071.7 Reference GRCm39 C57BL/6J

      Range
      29519495..29520860
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein Strain
    Heading Accession and Version

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