RRC ID 61103
Author Aktar S, Sasaki H, Unoki M.
Title Identification of ZBTB24 protein domains and motifs for heterochromatin localization and transcriptional activation.
Journal Genes Cells
Abstract Immunodeficiency, centromeric instability, facial anomalies (ICF) syndrome is a rare autosomal recessive disorder caused by mutations in either DNMT3B, ZBTB24, CDCA7, HELLS or an unknown gene(s). Among the known causative genes, ZBTB24 encodes a member of the BTB-zinc finger (ZF) transcription factor family. The protein possesses a BTB domain, an AT-hook and eight C2H2 ZF motifs. All ZBTB24 mutations reported in ICF patients are predicted to disrupt at least one ZF motif. Here, we show that both AT-hook and distinct ZF motifs, particularly the 6th motif, of human and mouse ZBTB24 proteins are important for their heterochromatin localization. On the other hand, the 6th and 7th ZF motifs, and not the AT-hook or the BTB domain, of the human and mouse proteins are essential for transcriptional activation of CDCA7, another ICF causative gene and a known target of ZBTB24. By deletion analysis of the human CDCA7 promoter, we show that two motifs for ZBTB24 binding are important for transcriptional activation of this gene. These results reveal the evolutionarily conserved domains and motifs important for the biological function of ZBTB24, which provides a basis for understanding the molecular mechanisms underlying the pathogenesis of ICF syndrome.
Volume 24(11)
Pages 746-755
Published 2019-11-1
DOI 10.1111/gtc.12723
PMID 31561277
MeSH Amino Acid Motifs* Animals CYS2-HIS2 Zinc Fingers Face / abnormalities HEK293 Cells Heterochromatin* Humans Mice Mutation NIH 3T3 Cells Nuclear Proteins Primary Immunodeficiency Diseases / genetics Protein Binding Protein Domains* Repressor Proteins / chemistry* Repressor Proteins / genetics Repressor Proteins / isolation & purification* Repressor Proteins / metabolism Transcription Factors / metabolism Transcriptional Activation* Zinc Fingers
IF 1.922
Resource
DNA material Human CDCA7 promoter P1 (RDB18159) Human CDCA7 promoter P2 (RDB18160) Human CDCA7 promoter P2M (RDB18161) Human CDCA7 promoter P3 (RDB18162) Human CDCA7 promoter P4 (RDB18163) Human CDCA7 promoter P4M (RDB18164) Human CDCA7 promoter P5 (RDB18165) Human OSTC promoter P1 (RDB18166) Human OSTC promoter P1M (RDB18167) Human OSTC promoter P1DM (RDB18168) Mouse Cdca7 promoter P1 (RDB18169) EGFP-ZBTB24 deltaBTB (mouse) (RDB18171) EGFP-ZBTB24 deltaAT (mouse) (RDB18172) EGFP-ZBTB24 deltaZF (mouse) (RDB18173) EGFP-ZBTB24 mutAT (mouse) (RDB18174) EGFP-ZBTB24 mutZF1 (mouse) (RDB18175) EGFP-ZBTB24 mutZF2 (mouse) (RDB18176) EGFP-ZBTB24 mutZF3 (mouse) (RDB18177) EGFP-ZBTB24 mutZF4 (mouse) (RDB18178) EGFP-ZBTB24 mutZF5 (mouse) (RDB18179) EGFP-ZBTB24 mutZF6 (mouse) (RDB18180) EGFP-ZBTB24 mutZF7 (mouse) (RDB18181) EGFP-ZBTB24 mutZF8 (mouse) (RDB18182) EGFP-ZBTB24 mutCAKUT (mouse) (RDB18183) EGFP-ZBTB24 deltaBTB (human) (RDB18185) EGFP-ZBTB24 deltaAT (human) (RDB18186) EGFP-ZBTB24 deltaZF (human) (RDB18187) EGFP-ZBTB24 mutAT (human) (RDB18188) EGFP-ZBTB24 mutZF1 (human) (RDB18189) EGFP-ZBTB24 mutZF2 (human) (RDB18190) EGFP-ZBTB24 mutZF3 (human) (RDB18191) EGFP-ZBTB24 mutZF4 (human) (RDB18192) EGFP-ZBTB24 mutZF5 (human) (RDB18193) EGFP-ZBTB24 mutZF6 (human) (RDB18194) EGFP-ZBTB24 mutZF7 (human) (RDB18195) EGFP-ZBTB24 mutZF8 (human) (RDB18196) EGFP-ZBTB24 mutCAKUT (human) (RDB18197)