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TitleThe C-Terminal Zinc Fingers of ZBTB38 are Novel Selective Readers of DNA Methylation.
Journal, issue, pagesJ Mol Biol, Vol. 430, Issue 3, Page 258-271, Year 2018
Publish dateFeb 2, 2018
AuthorsAmir Pozner / Nicholas O Hudson / Jill Trewhella / Tommy W Terooatea / Sven A Miller / Bethany A Buck-Koehntop /
PubMed AbstractMethyl-CpG binding proteins play an essential role in translating DNA methylation marks into a downstream transcriptional response, which has implications for both normal cell function as well as ...Methyl-CpG binding proteins play an essential role in translating DNA methylation marks into a downstream transcriptional response, which has implications for both normal cell function as well as disease. Although for many of these proteins, a detailed mechanistic understanding for how this cellular process is mediated remains to be determined. ZBTB38 is an under-characterized member of the zinc finger (ZF) family of methyl-CpG binding proteins. Functional knowledge has been gained for its conserved methylated DNA binding N-terminal ZF region; however, a specific role for the C-terminal set of five ZFs remains to be elucidated. Here we demonstrate for the first time that a subset of the C-terminal ZBTB38 ZFs exhibit high-affinity DNA interactions and that preferential targeting of the consensus DNA site is methyl specific. Utilizing a hybrid approach, a model for the C-terminal ZBTB38 ZFs in complex with its cognate DNA target is proposed, providing insight into a possible novel mode of methylated DNA recognition. Furthermore, it is shown that the C-terminal ZFs of ZBTB38 can directly occupy promoters harboring the newly identified sequence motif in cell in a methyl-dependent manner and, depending on the gene context, contribute to modulating transcriptional response. Combined, these findings provide evidence for a key and novel physiological function for the C-terminal ZF domain of ZBTB38.
External linksJ Mol Biol / PubMed:29287967
MethodsSAS (X-ray in house)
Structure data

SASDCA3:
Zinc finger and BTB domain-containing protein 38 (ZBTB38) complexed with methylated C-terminal ZBTB38 binding sequence
Method: SAXS/SANS

SASDCB3:
Methylated C-terminal ZBTB38 binding sequence (mCZ38BS)
Method: SAXS/SANS

Source
  • Homo sapiens (human)

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