C/EBPβ (CEBPB) protein binding to the C/EBP|CRE DNA 8-mer TTGC|GTCA is inhibited by 5hmC and enhanced by 5mC, 5fC, and 5caC in the CG dinucleotide

Khund-Sayeed, Syed; Zhao, Jianfei; Sathyanarayana, Bangalore K.; Golla, Jaya Prakash; Vinson, Charles

doi:10.1016/j.bbagrm.2015.03.002

Cited by 40 publications

(39 citation statements)

References 56 publications

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“…Single-stranded DNA 60-mers on microarrays were double stranded with: 1) cytosine, producing dsDNA with cytosine in both strands (DNA(C∣C)), 2) 5mC ( M ), producing dsDNA with 5mC in one strand and cytosine in the second strand (DNA(5mC∣C)), or 3) 5hmC ( H ), producing DNA(5hmC∣C) [8, 18, 20]. A fourth type of dsDNA was generated by enzymatic methylation of the two cytosines in all CG dinucleotides (one cytosine on each strand) [17].…”

Section: Resultsmentioning

confidence: 99%

Replacing C189 in the bZIP domain of Zta with S, T, V, or A changes DNA binding specificity to four types of double-stranded DNA

Ray

Tillo

Assad

et al. 2018

Biochemical and Biophysical Research Communications

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Zta is a bZIP transcription factor (TF) in the Epstein-Barr virus that binds unmethylated and methylated DNA sequences. Substitution of cysteine 189 of Zta to serine (Zta(C189S)) results in a virus that is unable to execute the lytic cycle, which was attributed to a change in binding to methylated DNA sequences. To learn more about the role of this position in defining sequence-specific DNA binding, we mutated cysteine 189 to four other amino acids, producing Zta(C189S), Zta(C189T), Zta(C189A), and Zta(C189V) mutants. Zta and mutants were used in protein binding microarray (PBM) experiments to evaluate sequence-specific DNA binding to four types of double-stranded DNA (dsDNA): 1) with cytosine in both strands (DNA(C|C)), 2) with 5-methylcytosine (5mC) in one strand and cytosine in the second strand (DNA(5mC|C)), 3) with 5-hydroxymethylcytosine (5hmC) in one strand and cytosine in the second strand (DNA(5hmC|C)), and 4) with both cytosines in all CG dinucleotides containing 5mC (DNA(5mCG)). Zta(C189S) and Zta(C189T) bound the TRE (AP-1) motif (TGA/TCA) more strongly than wild-type Zta, while binding to other sequences, including the C/EBP half site GCAA was reduced. Binding of Zta(C189S) and Zta(C189T) to DNA containing modified cytosines (DNA(5mC|C), DNA(5hmC|C), and DNA(5mCG)) was reduced compared to Zta. Zta(C189A) and Zta(C189V) had higher non-specific binding to all four types of DNA. Our data suggests that position C189 in Zta impacts sequence-specific binding to DNA containing modified and unmodified cytosine.

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Section: Resultsmentioning

confidence: 99%

Replacing C189 in the bZIP domain of Zta with S, T, V, or A changes DNA binding specificity to four types of double-stranded DNA

Ray

Tillo

Assad

et al. 2018

Biochemical and Biophysical Research Communications

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“…Methylation of DNA CpG motifs alters the DNA binding specificity of transcription factor complexes [82,83]. Both CRE elements (5′-TGACGTCA-3′) and some CAREs (consensus 5′-TGATGX 1 AAX 2 -3′, where X 1 = C) contain a central GC motif and may be subject to methylation [6,24].…”

Section: The Emerging Role Of Epigenetic Modifications In Controllingmentioning

confidence: 99%

Surviving Stress: Modulation of ATF4-Mediated Stress Responses in Normal and Malignant Cells

Wortel

Meer

Kilberg

et al. 2017

Trends in Endocrinology & Metabolism

415

364

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Activating transcription factor 4 (ATF4) is a stress-induced transcription factor that is frequently upregulated in cancer cells. ATF4 controls the expression of a wide range of adaptive genes that allow cells to endure periods of stress, such as hypoxia or amino acid limitation. However, under persistent stress conditions, ATF4 promotes the induction of apoptosis. Recent advances point to a role for post-translational modifications (PTMs) and epigenetic mechanisms in balancing these pro- and anti-survival effects of ATF4. We review here how PTMs and epigenetic modifiers associated with ATF4 may be exploited by cancer cells to cope with cellular stress conditions that are intrinsically associated with tumor growth. Identification of mechanisms that modulate ATF4-mediated transcription and its effects on cellular metabolism may uncover new targets for cancer treatment.

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“…In contrast, 5fC and 5caC are found at much lower levels at steady state (1–10% that of 5hmC), and preferentially accumulate at enhancers and other distal regulatory regions in the absence of TDG (13–18), implying that the dynamic turnover of 5mC may be particularly important in enhancer function. Recent work by our group and others showing that the binding of certain transcription factors to DNA is influenced by the presence of oxidized 5mC bases in vitro (19–23) and that 5fC/5caC pose a barrier to transcriptional elongation in cells (24) raise the question of whether 5fC/5caC may have functions in gene regulation beyond that of intermediates in the DNA demethylation cycle.…”

Section: Introductionmentioning

confidence: 99%

MAX is an epigenetic sensor of 5-carboxylcytosine and is altered in multiple myeloma

Wang

Hashimoto

Zhang

et al. 2016

Nucleic Acids Research

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The oncogenic transcription factor MYC and its binding partner MAX regulate gene expression by binding to DNA at enhancer-box (E-box) elements 5΄-CACGTG-3΄. In mammalian genomes, the central E-box CpG has the potential to be methylated at the 5-position of cytosine (5mC), or to undergo further oxidation to the 5-hydroxymethyl (5hmC), 5-formyl (5fC), or 5-carboxyl (5caC) forms. We find that MAX exhibits the greatest affinity for a 5caC or unmodified C-containing E-box, and much reduced affinities for the corresponding 5mC, 5hmC or 5fC forms. Crystallization of MAX with a 5caC modified E-box oligonucleotide revealed that MAX Arg36 recognizes 5caC using a 5caC–Arg–Guanine triad, with the next nearest residue to the carboxylate group being Arg60. In an analysis of >800 primary multiple myelomas, MAX alterations occurred at a frequency of ∼3%, more than half of which were single nucleotide substitutions affecting a basic clamp-like interface important for DNA interaction. Among these, arginines 35, 36 and 60 were the most frequently altered. In vitro binding studies showed that whereas mutation of Arg36 (R36W) or Arg35 (R35H/L) completely abolished DNA binding, mutation of Arg60 (R60Q) significantly reduced DNA binding, but retained a preference for the 5caC modified E-box. Interestingly, MAX alterations define a subset of myeloma patients with lower MYC expression and a better overall prognosis. Together these data indicate that MAX can act as a direct epigenetic sensor of E-box cytosine modification states and that local CpG modification and MAX variants converge to modulate the MAX-MYC transcriptional network.

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C/EBPβ (CEBPB) protein binding to the C/EBP|CRE DNA 8-mer TTGC|GTCA is inhibited by 5hmC and enhanced by 5mC, 5fC, and 5caC in the CG dinucleotide

Cited by 40 publications

References 56 publications

Replacing C189 in the bZIP domain of Zta with S, T, V, or A changes DNA binding specificity to four types of double-stranded DNA

Replacing C189 in the bZIP domain of Zta with S, T, V, or A changes DNA binding specificity to four types of double-stranded DNA

Surviving Stress: Modulation of ATF4-Mediated Stress Responses in Normal and Malignant Cells

MAX is an epigenetic sensor of 5-carboxylcytosine and is altered in multiple myeloma

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