A CpG island promoter drives the CXXC5 gene expression
Abstract CXXC5 is a member of the zinc-finger CXXC family that binds to unmethylated CpG dinucleotides. CXXC5 modulates gene expressions resulting in diverse cellular events mediated by distinct signaling pathways. However, the mechanism responsible for CXXC5 expression remains largely unknown. We f...
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2021
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oai:doaj.org-article:3dfa5821e414403e9650cdc17758dc3d2021-12-02T18:49:23ZA CpG island promoter drives the CXXC5 gene expression10.1038/s41598-021-95165-62045-2322https://doaj.org/article/3dfa5821e414403e9650cdc17758dc3d2021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95165-6https://doaj.org/toc/2045-2322Abstract CXXC5 is a member of the zinc-finger CXXC family that binds to unmethylated CpG dinucleotides. CXXC5 modulates gene expressions resulting in diverse cellular events mediated by distinct signaling pathways. However, the mechanism responsible for CXXC5 expression remains largely unknown. We found here that of the 14 annotated CXXC5 transcripts with distinct 5′ untranslated regions encoding the same protein, transcript variant 2 with the highest expression level among variants represents the main transcript in cell models. The DNA segment in and at the immediate 5′-sequences of the first exon of variant 2 contains a core promoter within which multiple transcription start sites are present. Residing in a region with high G–C nucleotide content and CpG repeats, the core promoter is unmethylated, deficient in nucleosomes, and associated with active RNA polymerase-II. These findings suggest that a CpG island promoter drives CXXC5 expression. Promoter pull-down revealed the association of various transcription factors (TFs) and transcription co-regulatory proteins, as well as proteins involved in histone/chromatin, DNA, and RNA processing with the core promoter. Of the TFs, we verified that ELF1 and MAZ contribute to CXXC5 expression. Moreover, the first exon of variant 2 may contain a G-quadruplex forming region that could modulate CXXC5 expression.Pelin YaşarGizem KarsKerim YavuzGamze AyazÇerağ OğuztüzünEcenaz BilgenZeynep SuvacıÖzgül Persil ÇetinkolTolga CanMesut MuyanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-20 (2021) |
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Medicine R Science Q Pelin Yaşar Gizem Kars Kerim Yavuz Gamze Ayaz Çerağ Oğuztüzün Ecenaz Bilgen Zeynep Suvacı Özgül Persil Çetinkol Tolga Can Mesut Muyan A CpG island promoter drives the CXXC5 gene expression |
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Abstract CXXC5 is a member of the zinc-finger CXXC family that binds to unmethylated CpG dinucleotides. CXXC5 modulates gene expressions resulting in diverse cellular events mediated by distinct signaling pathways. However, the mechanism responsible for CXXC5 expression remains largely unknown. We found here that of the 14 annotated CXXC5 transcripts with distinct 5′ untranslated regions encoding the same protein, transcript variant 2 with the highest expression level among variants represents the main transcript in cell models. The DNA segment in and at the immediate 5′-sequences of the first exon of variant 2 contains a core promoter within which multiple transcription start sites are present. Residing in a region with high G–C nucleotide content and CpG repeats, the core promoter is unmethylated, deficient in nucleosomes, and associated with active RNA polymerase-II. These findings suggest that a CpG island promoter drives CXXC5 expression. Promoter pull-down revealed the association of various transcription factors (TFs) and transcription co-regulatory proteins, as well as proteins involved in histone/chromatin, DNA, and RNA processing with the core promoter. Of the TFs, we verified that ELF1 and MAZ contribute to CXXC5 expression. Moreover, the first exon of variant 2 may contain a G-quadruplex forming region that could modulate CXXC5 expression. |
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Pelin Yaşar Gizem Kars Kerim Yavuz Gamze Ayaz Çerağ Oğuztüzün Ecenaz Bilgen Zeynep Suvacı Özgül Persil Çetinkol Tolga Can Mesut Muyan |
author_facet |
Pelin Yaşar Gizem Kars Kerim Yavuz Gamze Ayaz Çerağ Oğuztüzün Ecenaz Bilgen Zeynep Suvacı Özgül Persil Çetinkol Tolga Can Mesut Muyan |
author_sort |
Pelin Yaşar |
title |
A CpG island promoter drives the CXXC5 gene expression |
title_short |
A CpG island promoter drives the CXXC5 gene expression |
title_full |
A CpG island promoter drives the CXXC5 gene expression |
title_fullStr |
A CpG island promoter drives the CXXC5 gene expression |
title_full_unstemmed |
A CpG island promoter drives the CXXC5 gene expression |
title_sort |
cpg island promoter drives the cxxc5 gene expression |
publisher |
Nature Portfolio |
publishDate |
2021 |
url |
https://doaj.org/article/3dfa5821e414403e9650cdc17758dc3d |
work_keys_str_mv |
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