GeneID: 289

Description:
LYAR (Ly1 antibody reactive) is a zinc-finger transcription factor that binds to the 5'-GGTTAT-3' region of the 5' UTR of the Aγ-globin gene. It directly interacts with and recruits the methyltransferase PRMT5, which induces the repressive epigenetic mark H4R3me2s, in turn silencing γ-globin gene expression. LYAR knockdown leads to reactivation of embryonic β-like globin genes in MEL cells and to reactivation of foetal haemoglobin (Hb F) in human erythroid cells. The rs368698783 G>A polymorphism [IthaID: 2945] resides in the LYAR-binding site of the Aγ-globin gene, attenuating binding of LYAR and its complexes to the target DNA sequence. Experimental work has shown that this polymorphism associates with high basal and induced production of foetal haemoglobin (HbF) in β-thalassaemia patients.

Synonyms: ZC2HC2 , ZLYAR

Comments:
N/A

Number of entries/variants: 0

1. Ju J, Wang Y, Liu R, Zhang Y, Xu Z, Wang Y, Wu Y, Liu M, Cerruti L, Zou F, Ma C, Fang M, Tan R, Jane SM, Zhao Q, Human fetal globin gene expression is regulated by LYAR., Nucleic Acids Res., 42(15), 9740-52, 2014 PubMed
2. Chen D, Zuo Y, Zhang X, Ye Y, Bao X, Huang H, Tepakhan W, Wang L, Ju J, Chen G, Zheng M, Liu D, Huang S, Zong L, Li C, Chen Y, Zheng C, Shi L, Zhao Q, Wu Q, Fucharoen S, Zhao C, Xu X, A Genetic Variant Ameliorates β-Thalassemia Severity by Epigenetic-Mediated Elevation of Human Fetal Hemoglobin Expression., Am. J. Hum. Genet. , 101(1), 130-138, 2017 PubMed
3. Gemmo C, Breveglieri G, Marzaro G, Lampronti I, Cosenza LC, Gasparello J, Zuccato C, Fabbri E, Borgatti M, Chilin A, Finotti A, Gambari R, Surface plasmon resonance based analysis of the binding of LYAR protein to the rs368698783 (G>A) polymorphic Aγ-globin gene sequences mutated in β-thalassemia., Anal Bioanal Chem, 2019 PubMed
4. Zuccato C, Cosenza LC, Zurlo M, Breveglieri G, Bianchi N, Lampronti I, Gasparello J, Scapoli C, Borgatti M, Finotti A, Gambari R, The rs368698783 (G>A) Polymorphism Affecting LYAR Binding to the Gene Is Associated with High Fetal Hemoglobin (HbF) in β-Thalassemia Erythroid Precursor Cells Treated with HbF Inducers., Int J Mol Sci, 24(1), 0, 2023 PubMed