TBX20

Last updated
TBX20
Identifiers
Aliases TBX20 , T-box 20, ASD4, T-box transcription factor 20
External IDs OMIM: 606061 MGI: 1888496 HomoloGene: 32476 GeneCards: TBX20
Orthologs
SpeciesHumanMouse
Entrez

57057

57246

Ensembl

ENSG00000164532

ENSMUSG00000031965

UniProt

Q9UMR3

Q9ES03

RefSeq (mRNA)

NM_020417
NM_001077653
NM_001166220

NM_001205085
NM_020496
NM_194263

RefSeq (protein)

NP_001071121
NP_001159692

NP_001192014
NP_065242
NP_919239

Location (UCSC) Chr 7: 35.2 – 35.25 Mb Chr 9: 24.63 – 24.69 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

TBX20 (gene) is a member of the T-box family that encodes the transcription factor TBX20. Studies in mouse, human and fruitfly have shown that this gene is essential for early heart development, [5] [6] [7] [8] adult heart function [9] and yolk sac vasculature remodeling [7] and has been associated with congenital heart diseases. [10] [11] [12] Tbx20 was also shown to be required for migration of hindbrain motor neurons and in facial neurons was proposed to be a positive regulator of the non-canonical Wnt signaling pathway.

Contents

Tbx20 is a transcription factor that is essential for proper heart development in a growing fetus. Any mutations in this gene can result in various forms of congenital heart disease. One of the more serious examples is the presence of a septal defect. The interatrial septum is a piece of tissue that separates the left and right atria of the heart, which contain oxygenated and deoxygenated blood, respectively. In Tbx20 mutants, this divider does not form and results in deoxygenated blood flowing into the left atrium then left ventricle, which ships the blood to the organs and muscles. Since deoxygenated blood should not be delivered to the tissues, the result is cyanosis, or a bluish skin discoloration stemming from low oxygen concentration. Proper function of Tbx20 is essential because it controls other genes that regulate cardiomyocyte proliferation, such as Tbx2 and N-myc1. Cardiomyocytes are the basis for the correct architectural scheme of the heart, and if defects arise in these structures, proper heart development is likely unattainable. [13]

Embryonic heart functions

Tbx20 knockout mouse embryos die at around or before E10.5 with hypoplastic hearts. [5] [6] [7] [8]

This gene has been implicated in coordinating cardiac proliferation, regional specification [5] and formation of the cardiac chamber [6] [7] [8] Congenital heart diseases involving TBX20 include defects in septation, chamber growth and valvulogenesis [10] [11] and increased Tbx20 expression was shown to cause congenital atrial septal defects, patent foramen ovale and cardiac valve defects. [12]

Adult heart functions

In the fruitfly, knock-down of mid (midline), Drosophila's Tbx20 homolog gene, led to slower heart rate, arrythmias and abnormal myofibrillar architecture. [9] Heterozygous Tbx20 knockout adult mice displayed left ventricle dilation, decreased wall thickness and contractile abnormalities. [7] Homozygous conditional cardiomyocyte Tbx20 knockout adult mice died within 15 days after knockout induction. Mice hearts presented with dilated cardiomyopathy and contraction-related dysfunctions such as abnormal atrioventricular conduction, slower heart rate, altered ventricular depolarization/repolarization and arrhythmias. [14]

Known co-factors

Transcription factors GATA4 and NKX2-5 have been shown to physically interact with TBX20 and enhance gene expression. [7]

Known downstream gene targets

Tbx2 was shown to be directly repressed by Tbx20 in the myocardium. [5] [7] Analysis of data from genome-wide chromatin immunoprecipitation against TBX20 tagged with green fluorescent protein in adult (6–8 weeks) mouse whole heart, coupled with analysis of genes differentially expressed upon loss of Tbx20, identified hundreds of putative TBX20 direct targets. [14] [15]

Related Research Articles

<span class="mw-page-title-main">Mef2</span> Protein family

In the field of molecular biology, myocyte enhancer factor-2 (Mef2) proteins are a family of transcription factors which through control of gene expression are important regulators of cellular differentiation and consequently play a critical role in embryonic development. In adult organisms, Mef2 proteins mediate the stress response in some tissues. Mef2 proteins contain both MADS-box and Mef2 DNA-binding domains.

<span class="mw-page-title-main">GATA4</span> Protein-coding gene in the species Homo sapiens

Transcription factor GATA-4 is a protein that in humans is encoded by the GATA4 gene.

<span class="mw-page-title-main">PAX8</span> Mammalian protein found in humans

Paired box gene 8, also known as PAX8, is a protein which in humans is encoded by the PAX8 gene.

<span class="mw-page-title-main">PITX2</span> Protein-coding gene in the species Homo sapiens

Paired-like homeodomain transcription factor 2 also known as pituitary homeobox 2 is a protein that in humans is encoded by the PITX2 gene.

<span class="mw-page-title-main">Homeobox protein Nkx-2.5</span> Protein-coding gene in humans

Homeobox protein Nkx-2.5 is a protein that in humans is encoded by the NKX2-5 gene.

<span class="mw-page-title-main">GATA6</span> Protein-coding gene in the species Homo sapiens

Transcription factor GATA-6, also known as GATA-binding factor 6 (GATA6), is protein that in humans is encoded by the GATA6 gene. The gene product preferentially binds (A/T/C)GAT(A/T)(A) of the consensus binding sequence.

<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">ISL1</span> Protein-coding gene in the species Homo sapiens

Insulin gene enhancer protein ISL-1 is a protein that in humans is encoded by the ISL1 gene.

<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">HEY2</span> Protein-coding gene in the species Homo sapiens

Hairy/enhancer-of-split related with YRPW motif protein 2 (HEY2) also known as cardiovascular helix-loop-helix factor 1 (CHF1) is a protein that in humans is encoded by the HEY2 gene.

<span class="mw-page-title-main">Orthodenticle homeobox 2</span> Protein-coding gene in the species Homo sapiens

Homeobox protein OTX2 is a protein that in humans is encoded by the OTX2 gene.

<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">ZIC3</span> Protein-coding gene in the species Homo sapiens

ZIC3 is a member of the Zinc finger of the cerebellum (ZIC) protein family.

<span class="mw-page-title-main">HAND1</span> Protein-coding gene in the species Homo sapiens

Heart- and neural crest derivatives-expressed protein 1 is a protein that in humans is encoded by the HAND1 gene.

<span class="mw-page-title-main">HAND2</span> Protein-coding gene in the species Homo sapiens

Heart- and neural crest derivatives-expressed protein 2 is a protein that in humans is encoded by the HAND2 gene.

<span class="mw-page-title-main">ZFPM2</span> Protein-coding gene in the species Homo sapiens

Zinc finger protein ZFPM2, i.e. zinc finger protein, FOG family member 2, but also termed Friend of GATA2, Friend of GATA-2, FOG2, or FOG-2, is a protein that in humans is encoded by the ZFPM2 and in mice by the Zfpm2 gene.

<span class="mw-page-title-main">ALDH1A2</span> Protein-coding gene in the species Homo sapiens

Aldehyde dehydrogenase 1 family, member A2, also known as ALDH1A2 or retinaldehyde dehydrogenase 2 (RALDH2), is an enzyme that in humans is encoded by the ALDH1A2 gene.

<span class="mw-page-title-main">JARID2</span> Protein-coding gene in the species Homo sapiens

Protein Jumonji is a protein that in humans is encoded by the JARID2 gene. JARID2 is a member of the alpha-ketoglutarate-dependent hydroxylase superfamily.

Neural crest cells are multipotent cells required for the development of cells, tissues and organ systems. A subpopulation of neural crest cells are the cardiac neural crest complex. This complex refers to the cells found amongst the midotic placode and somite 3 destined to undergo epithelial-mesenchymal transformation and migration to the heart via pharyngeal arches 3, 4 and 6.

tinman, or tin is an Nk2-homeobox containing transcription factor first isolated in Drosophila flies. The human homolog is the Nkx2-5 gene. tinman is expressed in the precardiac mesoderm and is responsible for the differentiation, proliferation, and specification of cardiac progenitor cells. This gene is named after the character Tin Woodman who lacks a heart, as flies with nonfunctional tinman genes have cardiac deformities.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000164532 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000031965 - 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. 1 2 3 4 Cai CL, Zhou W, Yang L, Bu L, Qyang Y, Zhang X, Li X, Rosenfeld MG, Chen J, Evans S (May 2005). "T-box genes coordinate regional rates of proliferation and regional specification during cardiogenesis". Development. 132 (10): 2475–87. doi:10.1242/dev.01832. PMC   5576439 . PMID   15843407.
  6. 1 2 3 Singh MK, Christoffels VM, Dias JM, Trowe MO, Petry M, Schuster-Gossler K, Bürger A, Ericson J, Kispert A (Jun 2005). "Tbx20 is essential for cardiac chamber differentiation and repression of Tbx2". Development. 132 (12): 2697–707. doi:10.1242/dev.01854. PMID   15901664. S2CID   24077327.
  7. 1 2 3 4 5 6 7 Stennard FA, Costa MW, Lai D, Biben C, Furtado MB, Solloway MJ, McCulley DJ, Leimena C, Preis JI, Dunwoodie SL, Elliott DE, Prall OW, Black BL, Fatkin D, Harvey RP (May 2005). "Murine T-box transcription factor Tbx20 acts as a repressor during heart development, and is essential for adult heart integrity, function and adaptation". Development. 132 (10): 2451–62. doi: 10.1242/dev.01799 . PMID   15843414.
  8. 1 2 3 Takeuchi JK, Mileikovskaia M, Koshiba-Takeuchi K, Heidt AB, Mori AD, Arruda EP, Gertsenstein M, Georges R, Davidson L, Mo R, Hui CC, Henkelman RM, Nemer M, Black BL, Nagy A, Bruneau BG (May 2005). "Tbx20 dose-dependently regulates transcription factor networks required for mouse heart and motoneuron development". Development. 132 (10): 2463–74. doi: 10.1242/dev.01827 . hdl: 10393/12782 . PMID   15843409.
  9. 1 2 Qian L, Mohapatra B, Akasaka T, Liu J, Ocorr K, Towbin JA, Bodmer R (Dec 2008). "Transcription factor neuromancer/TBX20 is required for cardiac function in Drosophila with implications for human heart disease". Proceedings of the National Academy of Sciences of the United States of America. 105 (50): 19833–8. Bibcode:2008PNAS..10519833Q. doi: 10.1073/pnas.0808705105 . PMC   2605007 . PMID   19074289.
  10. 1 2 Kirk EP, Sunde M, Costa MW, Rankin SA, Wolstein O, Castro ML, Butler TL, Hyun C, Guo G, Otway R, Mackay JP, Waddell LB, Cole AD, Hayward C, Keogh A, Macdonald P, Griffiths L, Fatkin D, Sholler GF, Zorn AM, Feneley MP, Winlaw DS, Harvey RP (Aug 2007). "Mutations in cardiac T-box factor gene TBX20 are associated with diverse cardiac pathologies, including defects of septation and valvulogenesis and cardiomyopathy". American Journal of Human Genetics. 81 (2): 280–91. doi:10.1086/519530. PMC   1950799 . PMID   17668378.
  11. 1 2 Liu C, Shen A, Li X, Jiao W, Zhang X, Li Z (1 November 2008). "T-box transcription factor TBX20 mutations in Chinese patients with congenital heart disease". European Journal of Medical Genetics. 51 (6): 580–7. doi:10.1016/j.ejmg.2008.09.001. PMID   18834961.
  12. 1 2 Posch MG, Gramlich M, Sunde M, Schmitt KR, Lee SH, Richter S, Kersten A, Perrot A, Panek AN, Al Khatib IH, Nemer G, Mégarbané A, Dietz R, Stiller B, Berger F, Harvey RP, Ozcelik C (Apr 2010). "A gain-of-function TBX20 mutation causes congenital atrial septal defects, patent foramen ovale and cardiac valve defects". Journal of Medical Genetics. 47 (4): 230–5. doi:10.1136/jmg.2009.069997. PMC   2981023 . PMID   19762328.
  13. ↑ Song MR, Shirasaki R, Cai CL, Ruiz EC, Evans SM, Lee SK, Pfaff SL (Dec 2006). "T-Box transcription factor Tbx20 regulates a genetic program for cranial motor neuron cell body migration". Development. 133 (24): 4945–55. doi:10.1242/dev.02694. PMC   5851594 . PMID   17119020.
  14. 1 2 Shen T, Aneas I, Sakabe N, Dirschinger RJ, Wang G, Smemo S, Westlund JM, Cheng H, Dalton N, Gu Y, Boogerd CJ, Cai CL, Peterson K, Chen J, Nobrega MA, Evans SM (Dec 2011). "Tbx20 regulates a genetic program essential to adult mouse cardiomyocyte function". The Journal of Clinical Investigation. 121 (12): 4640–54. doi:10.1172/JCI59472. PMC   3223071 . PMID   22080862.
  15. ↑ Sakabe NJ, Aneas I, Shen T, Shokri L, Park SY, Bulyk ML, Evans SM, Nobrega MA (May 2012). "Dual transcriptional activator and repressor roles of TBX20 regulate adult cardiac structure and function". Human Molecular Genetics. 21 (10): 2194–204. doi:10.1093/hmg/dds034. PMC   3335310 . PMID   22328084.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.