GeneID: 245

Description:
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

Comments:
N/A

Number of entries/variants: 0

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