T-box family of transcription factor-TBX5, insights in development and disease.
The T-box gene family refers to a group of transcription factors that share a highly conserved, sequence-specific DNA-binding domain (T-box) containing around 180-amino acids. According to HUGO gene nomenclature committee (HGNC), there are 18 T-box family members. These T-box genes have been implicated essential roles during embryogenesis and cardiac development, given their specific expression pattern in developing mammalian heart for several T-box genes, includingTBX5.TBX5is consisted of three transcriptional variants which cover 9 exons and encode two distinct isoforms that differ in N-terminus.TBX5is probably the most frequently studied T-box gene over the past decade due to the typical cardiac defects observed in Holt-Oram syndrome (HOS), which is caused byTBX5mutation. Most of the mutations are within exons 3-7 where locate sequence coding for the T-box domain. Notably, a variety of cardiac defects, as well as abnormalities in limb and other organs have been seen in HOS syndrome with different kinds ofTBX5mutations, suggesting a heterogeneous disease mechanism. We have performed a meta-analysis ofTBX5and found a significant correlation between its single nucleotide polymorphism (SNP) rs3825214 (A to G), and risk of atrial fibrillation and its subtypes, supporting TBX5 as a master transcription factor for cardiac development. In addition, bioinformatics analysis of this SNP identified several TFs that may be affected for their binding affinity with TBX5. Identification and characterization of moreTBX5mutations and SNPs hold promise for therapeutic strategy targeting TBX5 associated developmental abnormalities and diseases.
Department of Hematological Laboratory Science, Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University Zhenjiang 212013, Jiangsu, China.
Ting
T
Zhu
The Center for Reproduction and Genetics, Suzhou Hospital Affiliated to Nanjing Medical University Suzhou, Jiangsu 215008, China.
Longwei
L
Qiao
Department of Hematological Laboratory Science, Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University Zhenjiang 212013, Jiangsu, China.
Qian
Q
Wang
Department of Hematological Laboratory Science, Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University Zhenjiang 212013, Jiangsu, China.
Rui
R
Mi
Department of Hematological Laboratory Science, Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University Zhenjiang 212013, Jiangsu, China.
Jinnan
J
Chen
Department of Hematological Laboratory Science, Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University Zhenjiang 212013, Jiangsu, China.
Yaojuan
Y
Lu
Department of Hematological Laboratory Science, Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University Zhenjiang 212013, Jiangsu, China.
Junxia
J
Gu
Department of Hematological Laboratory Science, Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University Zhenjiang 212013, Jiangsu, China.
Qiping
Q
Zheng
Holt-Oram syndrome; SNP rs3825214; T-box gene TBX5 mutation; atrial fibrillation; meta-analysis