Multimeric transcription factor BCL11A utilizes two zinc-finger tandem arrays to bind clustered short sequence motifs

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Апрель 17, 2025

BCL11A, a transcription factor, is vital for hematopoiesis, including B and T cell maturation the fetal-to-adult hemoglobin switch. Mutations in BCL11A are linked to neurodevelopmental disorders. contains two DNA-binding zinc-finger arrays, low-affinity ZF2-3 high-affinity ZF4-6, separated by 300-amino-acid linker. ZF4-5 share 73% identity, five out of six DNA base-interacting residues. These arrays bind similar short sequence motifs clusters, with linker enabling broader binding span. Crystallographic structures complex oligonucleotides from β-globin locus region, reveal recognition residues Asn756 (ZF4), Lys784 Arg787 (ZF5). A Lys784-to-Thr mutation, disorder persistent fetal globin expression, reduces over 10-fold but gains interaction variable base pair. isoforms may form oligomers, enhancing chromatin occupancy repressor functions allowing multiple copies both low- ZF DNA. distinctive properties, apparently conserved among vertebrates, provide essential functional flexibility this crucial regulator.

Язык: Английский

Expression, molecular mechanisms and therapeutic potentials of ATF1 in cancers

Life Sciences, Год журнала: 2024, Номер 360, С. 123256 - 123256

Опубликована: Ноя. 21, 2024

Язык: Английский