T-box

Last updated
T-box
1H6F.png
Crystallographic structure of the TBX3 protein dimer (cyan and green) complexed with DNA (brown) based on the PDB: 1h6f ​ coordinates.
Identifiers
SymbolT-box
Pfam PF00907
InterPro IPR001699
PROSITE PS50252
SCOP2 1xbr / SCOPe / SUPFAM
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary
PDB 1h6f ​, 1xbr ​

T-box refers to a group of transcription factors involved in embryonic limb and heart development. [1] Every T-box protein has a relatively large DNA-binding domain, generally comprising about a third of the entire protein that is both necessary and sufficient for sequence-specific DNA binding. All members of the T-box gene family bind to the "T-box", a DNA consensus sequence of TCACACCT. [2]

Contents

Members

T-boxes are especially important to the development of embryos, found in zebrafish oocyte by Bruce et al 2003 and Xenopus laevis oocyte by Xanthos et al 2001. They are also expressed in later stages, including adult mouse and rabbit studied by Szabo et al 2000. [3]

Mutations in the first one found caused short tails in mice, and thus the protein encoded was named brachyury, Greek for "short-tail". In mice this gene is named Tbxt, and in humans it is named TBXT . [4] [5] Brachyury has been found in all bilaterian animals that have been screened, and is also present in the cnidaria. [6]

The mouse Tbxt gene was cloned [7] and found to be a 436 amino acid embryonic nuclear transcription factor. The protein brachyury binds to the T-box through a region at its N-terminus.

Protein activity

The encoded proteins of TBX5 and TBX4 play a role in limb development, and play a major role in limb bud initiation specifically. [8] For instance, in chickens TBX4 specifies hindlimb status while Tbx5 specifies forelimb status. [9] The activation of these proteins by Hox genes initiates signaling cascades that involve the Wnt signaling pathway and FGF signals in limb buds. [8] Ultimately, TBX4 and TBX5 lead to the development of apical ectodermal ridge (AER) and zone of polarizing activity (ZPA) signaling centers in the developing limb bud, which specify the orientation growth of the developing limb. [8] Together, TBX5 and TBX4 play a role in patterning the soft tissues (muscles and tendons) of the musculoskeletal system. [10]

Defects

In humans, and some other animals, defects in the TBX5 gene expression are responsible for Holt–Oram syndrome, which is characterized by at least one abnormal wrist bone. Other arm bones are almost always affected, though the severity can vary widely, from complete absence of a bone, to only a reduction in bone length. [11] [12] Seventy-five percent of affected individuals also have heart defects, most often there is no separation between the left and right ventricle of the heart. [13]

TBX3 is associated with ulnar–mammary syndrome in humans, but is also responsible for the presence or absence of dun color in horses, and has no deleterious effects whether expressed or not. [14]

T-box genes

Genes encoding T-box proteins include:

See also

Related Research Articles

<span class="mw-page-title-main">TBX1</span> Protein-coding gene in the species Homo sapiens

T-box transcription factor TBX1 also known as T-box protein 1 and testis-specific T-box protein is a protein that in humans is encoded by the TBX1 gene. Genes in the T-box family are transcription factors that play important roles in the formation of tissues and organs during embryonic development. To carry out these roles, proteins made by this gene family bind to specific areas of DNA called T-box binding element (TBE) to control the expression of target genes.

<span class="mw-page-title-main">T-box transcription factor T</span> Protein-coding gene in the species Homo sapiens

T-box transcription factor T, also known as Brachyury protein, is encoded for in humans by the TBXT gene. Brachyury functions as a transcription factor within the T-box family of genes. Brachyury homologs have been found in all bilaterian animals that have been screened, as well as the freshwater cnidarian Hydra.

<span class="mw-page-title-main">GLI3</span> Protein-coding gene in the species Homo sapiens

Zinc finger protein GLI3 is a protein that in humans is encoded by the GLI3 gene.

<span class="mw-page-title-main">PAX6</span> Protein-coding gene in the species Homo sapiens

Paired box protein Pax-6, also known as aniridia type II protein (AN2) or oculorhombin, is a protein that in humans is encoded by the PAX6 gene.

<span class="mw-page-title-main">Holt–Oram syndrome</span> Medical condition

Holt–Oram syndrome is an autosomal dominant disorder that affects bones in the arms and hands and often causes heart problems. The syndrome may include an absent radial bone in the forearm, an atrial septal defect in the heart, or heart block. It affects approximately 1 in 100,000 people.

<span class="mw-page-title-main">Autoimmune regulator</span> Immune system protein

The autoimmune regulator (AIRE) is a protein that in humans is encoded by the AIRE gene. It is a 13kb gene on chromosome 21q22.3 that has 545 amino acids. AIRE is a transcription factor expressed in the medulla of the thymus. It is part of the mechanism which eliminates self-reactive T cells that would cause autoimmune disease. It exposes T cells to normal, healthy proteins from all parts of the body, and T cells that react to those proteins are destroyed.

<span class="mw-page-title-main">Limb development</span>

Limb development in vertebrates is an area of active research in both developmental and evolutionary biology, with much of the latter work focused on the transition from fin to limb.

The limb bud is a structure formed early in vertebrate limb development. As a result of interactions between the ectoderm and underlying mesoderm, formation occurs roughly around the fourth week of development. In the development of the human embryo the upper limb bud appears in the third week and the lower limb bud appears four days later.

<span class="mw-page-title-main">TCF4</span> Protein-coding gene in the species Homo sapiens

Transcription factor 4 (TCF-4) also known as immunoglobulin transcription factor 2 (ITF-2) is a protein that in humans is encoded by the TCF4 gene located on chromosome 18q21.2.

<span class="mw-page-title-main">CHD7</span> Protein-coding gene in the species Homo sapiens

Chromodomain-helicase-DNA-binding protein 7 also known as ATP-dependent helicase CHD7 is an enzyme that in humans is encoded by the CHD7 gene.

<span class="mw-page-title-main">FGF10</span> Protein-coding gene in the species Homo sapiens

Fibroblast growth factor 10 is a protein that in humans is encoded by the FGF10 gene.

<i>TBX5</i> (gene) Protein-coding gene that affects limb development and heart and bone function

T-box transcription factor TBX5, is a protein that in humans is encoded by the TBX5 gene. Abnormalities in the TBX5 gene can result in altered limb development, Holt-Oram syndrome, Tetra-amelia syndrome, and cardiac and skeletal problems.

<span class="mw-page-title-main">TBX3</span> Protein-coding gene in the species Homo sapiens

T-box transcription factor TBX3 is a protein that in humans is encoded by the TBX3 gene.

<span class="mw-page-title-main">SALL4</span> Protein-coding gene in the species Homo sapiens

Sal-like protein 4(SALL4) is a transcription factor encoded by a member of the Spalt-like (SALL) gene family, SALL4. The SALL genes were identified based on their sequence homology to Spalt, which is a homeotic gene originally cloned in Drosophila melanogaster that is important for terminal trunk structure formation in embryogenesis and imaginal disc development in the larval stages. There are four human SALL proteins with structural homology and playing diverse roles in embryonic development, kidney function, and cancer. The SALL4 gene encodes at least three isoforms, termed A, B, and C, through alternative splicing, with the A and B forms being the most studied. SALL4 can alter gene expression changes through its interaction with many co-factors and epigenetic complexes. It is also known as a key embryonic stem cell (ESC) factor.

<span class="mw-page-title-main">TBX2</span> Protein-coding gene in the species Homo sapiens

T-box transcription factor 2 Tbx2 is a transcription factor that is encoded by the Tbx2 gene on chromosome 17q21-22 in humans. This gene is a member of a phylogenetically conserved family of genes that share a common DNA-binding domain, the T-box. Tbx2 and Tbx3 are the only T-box transcription factors that act as transcriptional repressors rather than transcriptional activators, and are closely related in terms of development and tumorigenesis. This gene plays a significant role in embryonic and fetal development through control of gene expression, and also has implications in various cancers. Tbx2 is associated with numerous signaling pathways, BMP, TGFβ, Wnt, and FGF, which allow for patterning and proliferation during organogenesis in fetal development.

<span class="mw-page-title-main">TBX22</span> Protein-coding gene in the species Homo sapiens

T-box transcription factor TBX22 is a protein that in humans is encoded by the TBX22 gene.

<span class="mw-page-title-main">TBR1</span> Protein-coding gene in Homo sapiens

T-box, brain, 1 is a transcription factor protein important in vertebrate embryo development. It is encoded by the TBR1 gene. This gene is also known by several other names: T-Brain 1, TBR-1, TES-56, and MGC141978. TBR1 is a member of the TBR1 subfamily of T-box family transcription factors, which share a common DNA-binding domain. Other members of the TBR1 subfamily include EOMES and TBX21. TBR1 is involved in the differentiation and migration of neurons and is required for normal brain development. TBR1 interacts with various genes and proteins in order to regulate cortical development, specifically within layer VI of the developing six-layered human cortex. Studies show that TBR1 may play a role in major neurological diseases such as Alzheimer's disease (AD), Parkinson's disease (PD) and autism spectrum disorder (ASD).

<span class="mw-page-title-main">TBX6</span> Protein-coding gene in the species Homo sapiens

T-box 6 is a protein that in humans is encoded by the TBX6 gene.

T-box transcription factor Tbx4 is a transcription factor that belongs to T-box gene family that is involved in the regulation of embryonic developmental processes. The transcription factor is encoded by the TBX4 gene located on human chromosome 17. Tbx4 is known mostly for its role in the development of the hindlimb, but it also plays a critical role in the formation of the umbilicus. Tbx4 has been shown to be expressed in the allantois, hindlimb, lung and proctodeum.

<span class="mw-page-title-main">TBX15</span> Protein-coding gene in the species Homo sapiens

T-box transcription factor TBX15 is protein that is encoded in humans by the Tbx15 gene, mapped to Chromosome 3 in mice and Chromosome 1 in humans. Tbx15 is a transcription factor that plays a key role in embryonic development. Like other members of the T-box subfamily, Tbx15 is expressed in the notochord and primitive streak, where it assists with the formation and differentiation of the mesoderm. It is steadily downregulated after segmentation of the paraxial mesoderm.

References

  1. ↑ Wilson V, Conlon FL (2002). "The T-box family". Genome Biology. 3 (6): REVIEWS3008. doi:10.1186/gb-2002-3-6-reviews3008. PMC   139375 . PMID   12093383.
  2. ↑ Müller, CW; Herrmann, BG (23 October 1997). "Crystallographic structure of the T domain-DNA complex of the Brachyury transcription factor". Nature . 389 (6653): 884–8. Bibcode:1997Natur.389..884M. doi:10.1038/39929. PMID   9349824. S2CID   13138577.
  3. ↑ Naiche, L.A.; Harrelson, Zachary; Kelly, Robert G.; Papaioannou, Virginia E. (2005-12-01). "T-Box Genes in Vertebrate Development". Annual Review of Genetics . Annual Reviews. 39 (1): 219–239. doi:10.1146/annurev.genet.39.073003.105925. ISSN   0066-4197. PMID   16285859.
  4. ↑ "Entrez Gene: T".
  5. ↑ Edwards YH, Putt W, Lekoape KM, Stott D, Fox M, Hopkinson DA, Sowden J (March 1996). "The human homolog T of the mouse T(Brachyury) gene; gene structure, cDNA sequence, and assignment to chromosome 6q27". Genome Research. 6 (3): 226–33. doi: 10.1101/gr.6.3.226 . PMID   8963900.
  6. ↑ Scholz CB, Technau U (January 2003). "The ancestral role of Brachyury: expression of NemBra1 in the basal cnidarian Nematostella vectensis (Anthozoa)". Development Genes and Evolution. 212 (12): 563–70. doi:10.1007/s00427-002-0272-x. PMID   12536320. S2CID   25311702.
  7. ↑ Herrmann BG, Labeit S, Poustka A, King TR, Lehrach H (February 1990). "Cloning of the T gene required in mesoderm formation in the mouse". Nature. 343 (6259): 617–22. Bibcode:1990Natur.343..617H. doi:10.1038/343617a0. PMID   2154694. S2CID   4365020.
  8. 1 2 3 Tickle C (October 2015). "How the embryo makes a limb: determination, polarity and identity". Journal of Anatomy. 227 (4): 418–30. doi:10.1111/joa.12361. PMC   4580101 . PMID   26249743.
  9. ↑ Rodriguez-Esteban C, Tsukui T, Yonei S, Magallon J, Tamura K, Izpisua Belmonte JC (April 1999). "The T-box genes Tbx4 and Tbx5 regulate limb outgrowth and identity". Nature. 398 (6730): 814–8. Bibcode:1999Natur.398..814R. doi:10.1038/19769. PMID   10235264. S2CID   4330287.
  10. ↑ Hasson P, DeLaurier A, Bennett M, Grigorieva E, Naiche LA, Papaioannou VE, Mohun TJ, Logan MP (January 2010). "Tbx4 and tbx5 acting in connective tissue are required for limb muscle and tendon patterning". Developmental Cell. 18 (1): 148–56. doi:10.1016/j.devcel.2009.11.013. PMC   3034643 . PMID   20152185.
  11. ↑ "Holt–Oram syndrome". Genetics Home Reference. U.S. National Library of Medicine. June 2014. Retrieved 18 April 2018.
  12. ↑ McDermott DA, Fong JC, Basson CT. Holt–Oram Syndrome. 2004 Jul 20 [Updated 2015 Oct 8]. In Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2018. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1111/
  13. ↑ Bossert, T; Walther, T; Gummert, J; Hubald, R; Kostelka, M; Mohr, FW (October 2002). "Cardiac malformations associated with the Holt–Oram syndrome—report on a family and review of the literature". The Thoracic and Cardiovascular Surgeon. 50 (5): 312–4. doi:10.1055/s-2002-34573. PMID   12375192.
  14. ↑ Imsland F, McGowan K, Rubin CJ, Henegar C, Sundström E, Berglund J, et al. (February 2016). "Regulatory mutations in TBX3 disrupt asymmetric hair pigmentation that underlies Dun camouflage color in horses". Nature Genetics. 48 (2): 152–8. doi:10.1038/ng.3475. PMC   4731265 . PMID   26691985.

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