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. 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 uses its N-terminal BTB/POZ domain for interaction with components of the NuRD complex, independently of BCL11A, to repress γ-globin expression. In addition, ZBTB7A directly binds to the γ-globin gene promoter at the -200 site. It has an array of four ZFs and binds a 10-base-pair (bp) pyrimidine-rich site 5′-CCCCTTCCCC-3′ (or 3′-GGGGAAGGGG-5′ on the complementary strand), spanning nucleotides -203 to -194. ZF1 and ZF2 recognize the 5' C:G quadruple, and ZF4 contacts the 3' C:G quadruple. At least seven naturally occurring HPFH mutations are found within the -200 element that impair ZBTB7A DNA binding, with the most severe disruptions resulting from mutations in the base pairs recognized by ZF1 and ZF2. 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


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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 PubMed
  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 PubMed
  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 PubMed
  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 PubMed
  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 PubMed
  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 PubMed
  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 PubMed
  8. Yang Y, Ren R, Ly LC, Horton JR, Li F, Quinlan KGR, Crossley M, Shi Y, Cheng X, Structural basis for human ZBTB7A action at the fetal globin promoter., Cell Rep, 36(13), 109759, 2021 PubMed
Created on 2018-06-19 19:04:35, Last reviewed on 2021-11-02 16:38:40 (Show full history)

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