Context-dependent CpG methylation directs cell-specific binding of transcription factor ZBTB38. Issue 13 (9th December 2022)

• Record Type: Journal Article
• Authors: Marchal, Claire; Defossez, Pierre-Antoine; Miotto, Benoit
• Is Part Of: Epigenetics. Volume 17:Issue 13(2022)
• Page Start: 2122
• Page End: 2143
• Publication Date: 2022-12-09
• Subjects: DNA methylation -- zinc finger protein ZBTB38 -- E2F factor -- Alu repeats -- cell cycle; Epigenesis -- Periodicals; Epigenetica; 572.86505
• DOI: 10.1080/15592294.2022.2111135
• Languages: English
• ISSNs: 1559-2294

Abstract

ABSTRACT: DNA methylation on CpGs regulates transcription in mammals, both by decreasing the binding of methylation-repelled factors and by increasing the binding of methylation-attracted factors. Among the latter, zinc finger proteins have the potential to bind methylated CpGs in a sequence-specific context. The protein ZBTB38 is unique in that it has two independent sets of zinc fingers, which recognize two different methylated consensus sequences in vitro . Here, we identify the binding sites of ZBTB38 in a human cell line, and show that they contain the two methylated consensus sequences identified in vitro . In addition, we show that the distribution of ZBTB38 sites is highly unusual: while 10% of the ZBTB38 sites are also bound by CTCF, the other 90% of sites reside in closed chromatin and are not bound by any of the other factors mapped in our model cell line. Finally, a third of ZBTB38 sites are found upstream of long and active CpG islands. Our work therefore validates ZBTB38 as a methyl-DNA binder in vivo and identifies its unique distribution in the genome.