Qingyu Tang

Bio: Qingyu Tang is an academic researcher from North Carolina State University. The author has contributed to research in topics: Medicine & DNA. The author has an hindex of 4, co-authored 7 publications receiving 2240 citations. Previous affiliations of Qingyu Tang include Laboratory of Molecular Biology & Chinese Academy of Sciences.

Tet-Mediated Formation of 5-Carboxylcytosine and Its Excision by TDG in Mammalian DNA

Abstract: The prevalent DNA modification in higher organisms is the methylation of cytosine to 5-methylcytosine (5mC), which is partially converted to 5-hydroxymethylcytosine (5hmC) by the Tet (ten eleven translocation) family of dioxygenases. Despite their importance in epigenetic regulation, it is unclear how these cytosine modifications are reversed. Here, we demonstrate that 5mC and 5hmC in DNA are oxidized to 5-carboxylcytosine (5caC) by Tet dioxygenases in vitro and in cultured cells. 5caC is specifically recognized and excised by thymine-DNA glycosylase (TDG). Depletion of TDG in mouse embyronic stem cells leads to accumulation of 5caC to a readily detectable level. These data suggest that oxidation of 5mC by Tet proteins followed by TDG-mediated base excision of 5caC constitutes a pathway for active DNA demethylation.

Regulation of the histone acetyltransferase activity of hMOF via autoacetylation of Lys274

Abstract: Males-absent-on-the-first (MOF, also called MYST1 or KAT8) is a histone acetyltransferase (HAT) belonging to the MOZ, Ybf2/Sas3, Sas2 and Tip60 (MYST) family. MOF has been shown to possess a specific HAT activity towards Lys16 of histone H4 (H4K16) [1]. Homozygous knockout of MOF in mice results in loss of H4K16 acetylation and embryonic lethality, indicating that MOF and H4K16 acetylation are essential for embryogenesis and genome stability in mammals [2]. Downregulation of human MOF (hMOF) leads to dramatic nuclear morphological deformation and inhibition of cell cycle progression [3], and has recently been correlated with primary breast carcinoma and medulloblastoma [4]. Here we report the crystal structure of the catalytic domain (residues 174-449) of hMOF at 2.1 Å resolution (Figure 1 and Supplementary information, Data S1, Figure S1A and Table S1). Intriguingly, in the initial difference Fourier maps there was strong residual electron density at the tip of the side chain of Lys274 at the catalytic active site (Figure 1A, left panel). Modeling of the density as an acetyl group and further refinement of the acetylated Lys274 led to a good fit of the map (Figure 1A, right panel). Structural comparison indicates that the conformation of the catalytic domain of the apo hMOF is similar to that of hMOF in complex with acetylcoenzyme A (acetyl-CoA) alone (PDB code 2GIV) and in complex with acetyl-CoA and an male-specific lethal 1 (MSL1) fragment [5]. In particular, the acetylation of Lys274 is found in all these structures. The acetylation of Lys274 in the purified hMOF protein (hereafter the hMOF protein will refer to the catalytic domain of hMOF unless otherwise specified) was verified with liquid chromatography-tandem mass spectrometry (LC-MS/ MS) (Supplementary information, Figure S1B and S1C). Although other acetylation sites were also identified, the intensity of the peptide containing the acetylated Lys274 constituted 83% of the total intensity of the acetylated peptides, indicating that Lys274 is the major acetylation site (Supplementary information, Table S2). Furthernpg Cell Research (2011) 21:1262-1266. © 2011 IBCB, SIBS, CAS All rights reserved 1001-0602/11 $ 32.00 www.nature.com/cr

The Extracellular Domain of Pollen Receptor Kinase 3 is structurally similar to the SERK family of co-receptors.

Abstract: During reproduction in flowering plants, the male gametophyte delivers an immotile male gamete to the female gametophyte in the pistil by formation of pollen tubes. In Arabidopsis thaliana, two synergid cells situated on either side of the egg cell produce cysteine-rich chemoattractant peptide LURE that guides the pollen tube to the female gametophyte for sexual reproduction. Recently, in Arabidopsis thaliana, Pollen Receptor Kinase 3 (PRK3), along with PRK1, PRK6, and PRK8, have been predicted to be the receptors responsible for sensing LURE. These receptors belong to the Leucine Rich Repeat Receptor Like Kinases (LRR-RLKs), the largest family of receptor kinases found in Arabidopsis thaliana. How PRKs regulate the growth and development of the pollen tube remains elusive. In order to better understand the PRK-mediated signaling mechanism in pollen tube growth and guidance, we have determined the crystal structure of the extracellular domain (ecd) of PRK3 at 2.5 A, which resembles the SERK family of plant co-receptors. The structure of ecdPRK3 is composed of a conserved surface that coincides with the conserved receptor-binding surface of the SERK family of co-receptors. Our structural analyses of PRK3 have provided a template for future functional studies of the PRK family of LRR-RLK receptors in the regulation of pollen tube development.

Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine

Abstract: 5-methylcytosine (5mC) in DNA plays an important role in gene expression, genomic imprinting, and suppression of transposable elements. 5mC can be converted to 5-hydroxymethylcytosine (5hmC) by the Tet (ten eleven translocation) proteins. Here, we show that, in addition to 5hmC, the Tet proteins can generate 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) from 5mC in an enzymatic activity–dependent manner. Furthermore, we reveal the presence of 5fC and 5caC in genomic DNA of mouse embryonic stem cells and mouse organs. The genomic content of 5hmC, 5fC, and 5caC can be increased or reduced through overexpression or depletion of Tet proteins. Thus, we identify two previously unknown cytosine derivatives in genomic DNA as the products of Tet proteins. Our study raises the possibility that DNA demethylation may occur through Tet-catalyzed oxidation followed by decarboxylation.

The biogenesis, biology and characterization of circular RNAs.

Abstract: Circular RNAs (circRNAs) are covalently closed, endogenous biomolecules in eukaryotes with tissue-specific and cell-specific expression patterns, whose biogenesis is regulated by specific cis-acting elements and trans-acting factors. Some circRNAs are abundant and evolutionarily conserved, and many circRNAs exert important biological functions by acting as microRNA or protein inhibitors ('sponges'), by regulating protein function or by being translated themselves. Furthermore, circRNAs have been implicated in diseases such as diabetes mellitus, neurological disorders, cardiovascular diseases and cancer. Although the circular nature of these transcripts makes their detection, quantification and functional characterization challenging, recent advances in high-throughput RNA sequencing and circRNA-specific computational tools have driven the development of state-of-the-art approaches for their identification, and novel approaches to functional characterization are emerging.

The molecular hallmarks of epigenetic control

Abstract: Over the past 20 years, breakthrough discoveries of chromatin-modifying enzymes and associated mechanisms that alter chromatin in response to physiological or pathological signals have transformed our knowledge of epigenetics from a collection of curious biological phenomena to a functionally dissected research field. Here, we provide a personal perspective on the development of epigenetics, from its historical origins to what we define as 'the modern era of epigenetic research'. We primarily highlight key molecular mechanisms of and conceptual advances in epigenetic control that have changed our understanding of normal and perturbed development.