ZBTB24 is a transcriptional regulator that coordinates with DNMT3B to control DNA methylation

Joyce J. Thompson, Rupinder Kaur, Carlos P. Sosa, Jeong Heon Lee, Katsunobu Kashiwagi, Dan Zhou, Keith D Robertson

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

The interplay between transcription factors and epigenetic writers like the DNA methyltransferases (DNMTs), and the role of this interplay in gene expression, is being increasingly appreciated. ZBTB24, a poorly characterized zinc-finger protein, or the de novo methyltransferase DNMT3B, when mutated, cause Immunodeficiency, Centromere Instability, and Facial anomalies (ICF) syndrome, suggesting an underlying mechanistic link. Chromatin immunoprecipitation coupled with loss-of-function approaches in model systems revealed common loci bound by ZBTB24 and DNMT3B, where they function to regulate gene body methylation. Genes coordinately regulated by ZBTB24 and DNMT3B are enriched for molecular mechanisms essential for cellular homeostasis, highlighting the importance of the ZBTB24-DNMT3B interplay in maintaining epigenetic patterns required for normal cellular function. We identify a ZBTB24 DNA binding motif, which is contained within the promoters of most of its transcriptional targets, including CDCA7, AXIN2, and OSTC. Direct binding of ZBTB24 at the promoters of these genes targets them for transcriptional activation. ZBTB24 binding at the promoters of RNF169 and CAMKMT, however, targets them for transcriptional repression. The involvement of ZBTB24 targets in diverse cellular programs, including the VDR/RXR and interferon regulatory pathways, suggest that ZBTB24's role as a transcriptional regulator is not restricted to immune cells.

Original languageEnglish (US)
Pages (from-to)10034-10051
Number of pages18
JournalNucleic Acids Research
Volume46
Issue number19
DOIs
StatePublished - Nov 2 2018

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DNA Methylation
Methyltransferases
Epigenomics
Genes
Nucleotide Motifs
Centromere
Chromatin Immunoprecipitation
Zinc Fingers
Interferons
Methylation
Transcriptional Activation
Homeostasis
Transcription Factors
Gene Expression
DNA
Proteins

ASJC Scopus subject areas

  • Genetics

Cite this

ZBTB24 is a transcriptional regulator that coordinates with DNMT3B to control DNA methylation. / Thompson, Joyce J.; Kaur, Rupinder; Sosa, Carlos P.; Lee, Jeong Heon; Kashiwagi, Katsunobu; Zhou, Dan; Robertson, Keith D.

In: Nucleic Acids Research, Vol. 46, No. 19, 02.11.2018, p. 10034-10051.

Research output: Contribution to journalArticle

Thompson, Joyce J. ; Kaur, Rupinder ; Sosa, Carlos P. ; Lee, Jeong Heon ; Kashiwagi, Katsunobu ; Zhou, Dan ; Robertson, Keith D. / ZBTB24 is a transcriptional regulator that coordinates with DNMT3B to control DNA methylation. In: Nucleic Acids Research. 2018 ; Vol. 46, No. 19. pp. 10034-10051.
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