TSHZ1

Teashirt zinc finger homeobox 1 is a protein that in humans is encoded by the TSHZ1 gene.^[5]

TSHZ1
Identifiers
Aliases	TSHZ1, CAA, NY-CO-33, SDCCAG33, TSH1, teashirt zinc finger homeobox 1
External IDs	OMIM: 614427; MGI: 1346031; HomoloGene: 4227; GeneCards: TSHZ1; OMA:TSHZ1 - orthologs
Gene location (Human) Chr. Chromosome 18 (human)[1] Band 18q22.3 Start 75,210,755 bp[1] End 75,289,950 bp[1]
Gene location (Mouse) Chr. Chromosome 18 (mouse)[2] Band 18 E4|18 57.53 cM Start 84,029,752 bp[2] End 84,105,831 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in jejunal mucosa cerebellar vermis mucosa of ileum Brodmann area 23 endothelial cell pancreatic epithelial cell primary visual cortex caput epididymis middle temporal gyrus myocardium of left ventricle Top expressed in Rostral migratory stream olfactory bulb olfactory epithelium migratory enteric neural crest cell cumulus cell zygote abdominal wall vestibular membrane of cochlear duct ciliary body olfactory tubercle More reference expression data BioGPS n/a
Gene ontology Molecular function DNA binding metal ion binding chromatin binding DNA-binding transcription repressor activity, RNA polymerase II-specific nucleic acid binding DNA-binding transcription factor activity, RNA polymerase II-specific Cellular component nucleus Biological process soft palate development regulation of gene expression regulation of transcription, DNA-templated transcription, DNA-templated anterior/posterior pattern specification middle ear morphogenesis multicellular organism development regulation of transcription by RNA polymerase II negative regulation of transcription by RNA polymerase II Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 10194 110796 Ensembl ENSG00000179981 ENSMUSG00000046982 UniProt Q6ZSZ6 Q5DTH5 RefSeq (mRNA) NM_001308210 NM_005786 NM_001081300 NM_001364993 NM_001364994 RefSeq (protein) NP_001295139 NP_005777 NP_005777.3 NP_001074769 NP_001351922 NP_001351923 Location (UCSC) Chr 18: 75.21 – 75.29 Mb Chr 18: 84.03 – 84.11 Mb PubMed search [3] [4]
Wikidata
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Function

This gene encodes a colon cancer antigen that was defined by serological analysis of recombinant cDNA expression libraries. The encoded protein is a member of the teashirt C2H2-type zinc-finger protein family and may be involved in transcriptional regulation of developmental processes. Mutations in this gene may be associated with congenital aural atresia syndrome.

In Animal Models

In addition to humans, orthologous Tshz-family genes are known to exist in several other organisms, including invertebrates like insects. Research using model organisms can be majorly beneficial in exploring the potential functionality of genes that are present in humans without requiring human testing. Additionally, by looking at gene number and function changes between organisms with differing levels of relatedness, it is possible to gain a better understanding of the gene’s phylogeny, or evolutionary history. Findings related to Tshz1 orthologs in model organisms varies in scale and density of research from organism to organism.

In Mice

Mice are commonly used to study Tshz1 functionality due to their closer relatedness to humans as mammals compared to other common model organisms. However, Tshz1 genes in non-model mammalian organisms have been characterized, or explored in detail, to a limited extent. The Tshz1 ortholog in the Mus musculus mouse model has been implicated in motor neuron development^[6] and craniofacial morphogenesis.^[7]  Experiments involving whole gene knockout of Tshz1 during development resulted in universal lethality of M. musculus pups shortly after birth, presumably due to soft palate defects and skeletal deformities linked with Tshz1 inactivation.^[8] Mutant mice in knockout and loss of function experiments have been observed to be unable to suckle and feed, with their intestines filling up with air shortly after birth and their stomach appearing distended compared to wild type individuals.^[8] Investigations into Tshz1 impact on motor neuron development have been limited in scale, however Tshz1 mutant mice have been observed to have difficulties regulating breathing, due to decreased survival of Hypoglossal nerve and phrenic motor neurons during development.^[8]

In Zebrafish

Tshz1 orthologs in Danio rerio have largely yet to be characterized, however experiments using in-situ hybridization to mark gene expression have shown that Tshz1a is most highly expressed in the spinal cord, fore-to-hindbrain, and eye during early development.^[9] Consequently, it is suspected that Tshz1a may play a role in neuron development in the brain and visual system, including the retina.^[9] Three other Tshz family genes are known to exist in Zebrafish: Tshz2, Tshz3a, and Tshz3b. A fifth gene, Tshz1b, is predicted to exist.^[10] Multiple versions of the same gene commonly exist in the Zebrafish genome, referred to as ‘a’ and ‘b’, due to an evolutionary event known as WGD (Whole Genome Duplication) in the ancestral lineage of Teleost fish, which Zebrafish belong to.^[11] The potential existence of Tshz1b is therefore contingent on whether or not the Tshz1 ortholog in the Zebrafish ancestor existed prior to the WGD event/events, and if so, whether or not Tshz1b was lost subsequently over time due to chromosome rearrangement.

In Fruit Flies

Drosophila melanogaster is known to possess one Tshz family gene, commonly referred to as Tsh or T Shirt, and is known to be orthologous to the Tshz gene family in humans and other vertebrates.^[12] Tsh has been found to be involved in DNA-binding activity and several aspects of development, including formation of head structures^[13] and wing hinge development.^[14] Other important processes Tsh is involved in include segmental identity, dorsal/ventral patterning, and development of the compound eye.^[12] Additionally, Tsh has been used as a test gene for creating more streamlined methods for determining the position of enhancer elements due to its large ratio of non-coding RNAs.^[15] While distantly related to humans, the presence of a Tshz-family gene in D. melanogaster suggests that this gene family originates early in the evolutionary lineage of modern-day organisms, before the divergence of vertebrate and invertebrate eukaryotes. Currently, no non-eukaryotic organisms are known to possess a Tshz-orthologous gene, but several other invertebrates, such as Bactrocera latifrons^[16] and Ceratitis capitata^[17] have known Tsh orthologs.

References

1. GRCh38: Ensembl release 89: ENSG00000179981 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000046982 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: Teashirt zinc finger homeobox 1".
6. Chaimowicz C, Ruffault PL, Chéret C, Woehler A, Zampieri N, Fortin G, et al. (September 2019). "Teashirt 1 (Tshz1) is essential for the development, survival and function of hypoglossal and phrenic motor neurons in mouse". Development. 146 (17): dev.174045. doi:10.1242/dev.174045. PMC 6765129. PMID 31427287.
7. Melvin VS, Feng W, Hernandez-Lagunas L, Artinger KB, Williams T (July 2013). "A morpholino-based screen to identify novel genes involved in craniofacial morphogenesis". Developmental Dynamics. 242 (7): 817–831. doi:10.1002/dvdy.23969. PMC 4027977. PMID 23559552.
8. Coré N, Caubit X, Metchat A, Boned A, Djabali M, Fasano L (August 2007). "Tshz1 is required for axial skeleton, soft palate and middle ear development in mice". Developmental Biology. 308 (2): 407–420. doi:10.1016/j.ydbio.2007.05.038. PMID 17586487.
9. Wang H, Lee EM, Sperber SM, Lin S, Ekker M, Long Q (January 2007). "Isolation and expression of zebrafish zinc-finger transcription factor gene tsh1". Gene Expression Patterns. 7 (3): 318–322. doi:10.1016/j.modgep.2006.08.004. PMID 17035100.
10. Santos JS, Fonseca NA, Vieira CP, Vieira J, Casares F (March 2010). "Phylogeny of the teashirt-related zinc finger (tshz) gene family and analysis of the developmental expression of tshz2 and tshz3b in the zebrafish". Developmental Dynamics. 239 (3): 1010–1018. doi:10.1002/dvdy.22228. PMID 20108322. S2CID 27433898.
11. Glasauer SM, Neuhauss SC (December 2014). "Whole-genome duplication in teleost fishes and its evolutionary consequences" (PDF). Molecular Genetics and Genomics. 289 (6): 1045–1060. doi:10.1007/s00438-014-0889-2. PMID 25092473. S2CID 6425319.
12. Caubit X, Coré N, Boned A, Kerridge S, Djabali M, Fasano L (March 2000). "Vertebrate orthologues of the Drosophila region-specific patterning gene teashirt". Mechanisms of Development. 91 (1–2): 445–8. doi:10.1016/s0925-4773(99)00318-4. PMID 10704881. S2CID 6771237.
13. Bhojwani J, Shashidhara LS, Sinha P (August 1997). "Requirement of teashirt (tsh) function during cell fate specification in developing head structures in Drosophila". Development Genes and Evolution. 207 (3): 137–146. doi:10.1007/s004270050101. PMID 27747411. S2CID 10305055.
14. Soanes KH, MacKay JO, Core N, Heslip T, Kerridge S, Bell JB (July 2001). "Identification of a regulatory allele of teashirt (tsh) in Drosophila melanogaster that affects wing hinge development. An adult-specific tsh enhancer in Drosophila". Mechanisms of Development. 105 (1–2): 145–151. doi:10.1016/S0925-4773(01)00397-5. PMID 11429289. S2CID 14831771.
15. Voutev R, Mann RS (March 2016). "Streamlined scanning for enhancer elements in Drosophila melanogaster". BioTechniques. 60 (3): 141–144. doi:10.2144/000114391. PMC 5464965. PMID 26956092.
16. "Protein teashirt [Ceratitis capitata (Mediterranean fruit fly)]". Entrez Gene. National Center for Biotechnology Information (NCBI), U.S. National Library of Medicine.
17. "Protein teashirt [Bactrocera latifrons]". Entrez Gene. National Center for Biotechnology Information (NCBI), U.S. National Library of Medicine.

Further reading

• Schick B, Wemmert S, Willnecker V, Dlugaiczyk J, Nicolai P, Siwiec H, et al. (November 2011). "Genome-wide copy number profiling using a 100K SNP array reveals novel disease-related genes BORIS and TSHZ1 in juvenile angiofibroma". International Journal of Oncology. 39 (5): 1143–1151. doi:10.3892/ijo.2011.1166. PMID 21874228.
• Kajiwara Y, Akram A, Katsel P, Haroutunian V, Schmeidler J, Beecham G, et al. (2009). Bush AI (ed.). "FE65 binds Teashirt, inhibiting expression of the primate-specific caspase-4". PLOS ONE. 4 (4): e5071. Bibcode:2009PLoSO...4.5071K. doi:10.1371/journal.pone.0005071. PMC 2660419. PMID 19343227.
• Scanlan MJ, Chen YT, Williamson B, Gure AO, Stockert E, Gordan JD, et al. (May 1998). "Characterization of human colon cancer antigens recognized by autologous antibodies". International Journal of Cancer. 76 (5): 652–658. doi:10.1002/(SICI)1097-0215(19980529)76:5<652::AID-IJC7>3.0.CO;2-P. PMID 9610721. S2CID 916155.
• Coré N, Caubit X, Metchat A, Boned A, Djabali M, Fasano L (August 2007). "Tshz1 is required for axial skeleton, soft palate and middle ear development in mice". Developmental Biology. 308 (2): 407–420. doi:10.1016/j.ydbio.2007.05.038. PMID 17586487.
• Feenstra I, Vissers LE, Pennings RJ, Nillessen W, Pfundt R, Kunst HP, et al. (December 2011). "Disruption of teashirt zinc finger homeobox 1 is associated with congenital aural atresia in humans". American Journal of Human Genetics. 89 (6): 813–819. doi:10.1016/j.ajhg.2011.11.008. PMC 3234381. PMID 22152683.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.