GeneID: 245


Common Name: LRF Type: Gene
Chromosome: 19 (NC_000019.10) Locus: N/A
HUGO Symbol: ZBTB7A Full Name: zinc finger and BTB domain containing 7A
Exons: 3 Introns: 2

The ZBTB7A gene encodes LRF (lymphoma/leukemia-related factor), a member of the BTB/POZ and Krüppel (POK) family of transcription factors. This family of proteins is characterized by one or more C-terminal C2H2/Krüppel-type zinc finger DNA-binding domains and an N-terminal BTB/POZ domain that tethers transcriptional repressor complexes. The POK transcription factors are crucial regulators of haematopoietic lineage commitment and differentiation, and have been implicated in tumorigenesis. ZBTB7A/LRF plays a crucial role in B-cell lineage commitment and functions as a tumour suppressor by transcriptionally repressing glycolytic and oncogenic pathways. ZBTB7A/LRF is an important regulator of γ-globin gene expression in erythroid cells. It represses γ-globin expression by recruiting a unique NuRD repressor complex, independently of BCL11A. It directly binds the γ-globin gene promoters, and the cluster at -200 bp of HPFH-associated mutations disrupts binding of the zinc fingers of ZBTB7A. It is a target gene of the master erythroid transcription factor KLF1, and thus a promising target for therapeutic induction of HbF levels in patients with β-globinopathies.

Synonyms: LRF , pokemon , FBI1 , FBI-1 , TIP21 , ZBTB7 , ZNF857A


Publications / Origin

  1. Lee SU, Maeda T, POK/ZBTB proteins: an emerging family of proteins that regulate lymphoid development and function., Immunol. Rev. , 247(1), 107-19, 2012
  2. Liu XS, Haines JE, Mehanna EK, Genet MD, Ben-Sahra I, Asara JM, Manning BD, Yuan ZM, ZBTB7A acts as a tumor suppressor through the transcriptional repression of glycolysis., Genes Dev. , 28(17), 1917-28, 2014
  3. Liu XS, Chandramouly G, Rass E, Guan Y, Wang G, Hobbs RM, Rajendran A, Xie A, Shah JV, Davis AJ, Scully R, Lunardi A, Pandolfi PP, LRF maintains genome integrity by regulating the non-homologous end joining pathway of DNA repair., Nat Commun , 6(0), 8325, 2015
  4. Norton LJ, Funnell APW, Burdach J, Wienert B, Kurita R, Nakamura Y, Philipsen S, Pearson RCM, Quinlan KGR, Crossley M, KLF1 directly activates expression of the novel fetal globin repressor in erythroid cells., Blood Adv , 1(11), 685-692, 2017
  5. Zhu C, Chen G, Zhao Y, Gao XM, Wang J, Regulation of the Development and Function of B Cells by ZBTB Transcription Factors., Front Immunol , 9(0), 580, 2018
  6. Martyn GE, Wienert B, Yang L, Shah M, Norton LJ, Burdach J, Kurita R, Nakamura Y, Pearson RCM, Funnell APW, Quinlan KGR, Crossley M, Natural regulatory mutations elevate the fetal globin gene via disruption of BCL11A or ZBTB7A binding., Nat. Genet. , 50(4), 498-503, 2018
  7. Weber L, Frati G, Felix T, Hardouin G, Casini A, Wollenschlaeger C, Meneghini V, Masson C, De Cian A, Chalumeau A, Mavilio F, Amendola M, Andre-Schmutz I, Cereseto A, El Nemer W, Concordet JP, Giovannangeli C, Cavazzana M, Miccio A, Editing a γ-globin repressor binding site restores fetal hemoglobin synthesis and corrects the sickle cell disease phenotype., Sci Adv . , 6(7), 0, 2020
Created on 2018-06-19 19:04:35, Last reviewed on 2020-10-08 13:52:43 (Show full history)

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