Carboxylation of cytosine (5caC) in the CG dinucleotide in the E-box motif (CGCAG|GTG) increases binding of the Tcf3|Ascl1 helix-loop-helix heterodimer 10-fold

Golla, Jaya Prakash; Zhao, Jianfei; Mann, Ishminder; Sayeed, Syed K.; Mandal, Ajeet; Rose, Ray J.; Vinson, Charles

doi:10.1016/j.bbrc.2014.05.018

Cited by 20 publications

(20 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Wilms tumor protein 1 (WT1) physically interacts with Tet2 ( 36 , 37 ), either recruiting Tet2 to its target genes and/or binding to the ultimate product of the Tet2 enzyme, 5caC DNA ( 26 ). Additional examples of cytosine modification-specific effects on DNA binding factors include the stem cell factor Tcf3 ( 38 ). Furthermore, 5fC and 5caC in DNA retarded Pol II elongation on gene bodies and the polymerase formed specific hydrogen bonds with the 5-carboxyl group of 5caC ( 39 ).…”

Section: Discussionmentioning

confidence: 99%

Structure ofNaegleriaTet-like dioxygenase (NgTet1) in complexes with a reaction intermediate 5-hydroxymethylcytosine DNA

et al. 2015

View full text Add to dashboard Cite

The family of ten-eleven translocation (Tet) dioxygenases is widely distributed across the eukaryotic tree of life, from mammals to the amoeboflagellate Naegleria gruberi. Like mammalian Tet proteins, the Naegleria Tet-like protein, NgTet1, acts on 5-methylcytosine (5mC) and generates 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) in three consecutive, Fe(II)- and α-ketoglutarate-dependent oxidation reactions. The two intermediates, 5hmC and 5fC, could be considered either as the reaction product of the previous enzymatic cycle or the substrate for the next cycle. Here we present a new crystal structure of NgTet1 in complex with DNA containing a 5hmC. Along with the previously solved NgTet1–5mC structure, the two complexes offer a detailed picture of the active site at individual stages of the reaction cycle. In the crystal, the hydroxymethyl (OH-CH2-) moiety of 5hmC points to the metal center, representing the reaction product of 5mC hydroxylation. The hydroxyl oxygen atom could be rotated away from the metal center, to a hydrophobic pocket formed by Ala212, Val293 and Phe295. Such rotation turns the hydroxyl oxygen atom away from the product conformation, and exposes the target CH2 towards the metal-ligand water molecule, where a dioxygen O2 molecule would occupy to initiate the next round of reaction by abstracting a hydrogen atom from the substrate. The Ala212-to-Val (A212V) mutant profoundly limits the product to 5hmC, probably because the reduced hydrophobic pocket size restricts the binding of 5hmC as a substrate.

show abstract

Section: Discussionmentioning

confidence: 99%

Structure ofNaegleriaTet-like dioxygenase (NgTet1) in complexes with a reaction intermediate 5-hydroxymethylcytosine DNA

et al. 2015

View full text Add to dashboard Cite

show abstract

“…5caC has been observed to augment the interaction between basic helix-loop-helix (bHLH) family members and E-box sites. In other cases, the presence of 5caC at positions just flanking an E-box motif without a CpG substantially increased affinity of bHLH family members for this sequence [32,33], perhaps by altering DNA shape [34]. In other cases, modification of bases within the recognition sequence could promote binding or alter binding preference compared to unmodified DNA.…”

Section: Tet Proteins During Natural Differentiationmentioning

confidence: 99%

TET proteins in natural and induced differentiation

Scott‐Browne

Lio

Rao

2017

Current Opinion in Genetics & Development

View full text Add to dashboard Cite

The ten-eleven-translocation (TET) proteins oxidize 5-methylcytosine in DNA. Alterations in TET protein function have been linked to cancer, but TETs have also been observed to influence many cell differentiation processes. Here we review recent work assessing the contribution of TET proteins to natural and induced differentiation. Altogether these analyses have helped characterize how TETs and their enzymatic products influence DNA methylation patterns, regulatory element activity, DNA binding protein specificity and gene expression.

show abstract

“…Along with the previously mentioned MBD family proteins that recognize 5mC within the simple dinucleotide CpG sequence, certain mammalian zinc-finger family proteins such as Kaiso (Buck-Koehntop et al 2012), Zfp57 (Liu et al 2012), Klf4 (Liu et al 2014), and Egr1 (Hashimoto et al 2014a) bind 5mC within specific sequences via a common structural motif (Liu et al 2013; Hashimoto et al 2015b). In addition, another zinc-finger transcription factor WT1 (Hashimoto et al 2014a) and the basic helix-loop-helix (bHLH) family Tcf3-Ascl1 heterodimer (Golla et al 2014) can specifically bind 5caC within their consensus sequences. In prokaryotes, DpnI harbors a C-terminal winged-helix (WH) domain that recognizes the methyl group of N6mA within 5′-GATC-3′ sequence via Trp138 involving van der Waals interactions (Mierzejewska et al 2014).…”

Section: Base Flipping In the Recognition Of Modified Basesmentioning

confidence: 99%

DNA Base Flipping: A General Mechanism for Writing, Reading, and Erasing DNA Modifications

Hong

Cheng

2016

Advances in Experimental Medicine and Biology

View full text Add to dashboard Cite

The modification of DNA bases is a classic hallmark of epigenetics. Four forms of modified cytosine—5-methylcytosine, 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine—have been discovered in eukaryotic DNA. In addition to cytosine carbon-5 modifications, cytosine and adenine methylated in the exocyclic amine—N4-methylcytosine and N6-methyladenine—are other modified DNA bases discovered even earlier. Each modified base can be considered a distinct epigenetic signal with broader biological implications beyond simple chemical changes. Since 1994, crystal structures of proteins and enzymes involved in writing, reading, and erasing modified bases have become available. Here, we present a structural synopsis of writers, readers, and erasers of the modified bases from prokaryotes and eukaryotes. Despite significant differences in structures and functions, they are remarkably similar regarding their engagement in flipping a target base/nucleotide within DNA for specific recognitions and/or reactions. We thus highlight base flipping as a common structural framework broadly applied by distinct classes of proteins and enzymes across phyla for epigenetic regulations of DNA.

show abstract

Carboxylation of cytosine (5caC) in the CG dinucleotide in the E-box motif (CGCAG|GTG) increases binding of the Tcf3|Ascl1 helix-loop-helix heterodimer 10-fold

Cited by 20 publications

References 30 publications

Structure ofNaegleriaTet-like dioxygenase (NgTet1) in complexes with a reaction intermediate 5-hydroxymethylcytosine DNA

Structure ofNaegleriaTet-like dioxygenase (NgTet1) in complexes with a reaction intermediate 5-hydroxymethylcytosine DNA

TET proteins in natural and induced differentiation

DNA Base Flipping: A General Mechanism for Writing, Reading, and Erasing DNA Modifications

Contact Info

Product

Resources

About