CDK1 has been known to be the sole cyclin-dependent kinase (CDK) partner of cyclin B1 to drive mitotic progression. Here we demonstrate that CDK5 is active during mitosis and is necessary for maintaining mitotic fidelity. CDK5 is an atypical CDK owing to its high expression in post-mitotic neurons and activation by non-cyclin proteins p35 and p39.
View Article and Find Full Text PDFRepetitive sequences play an indispensable role in gene expression, transcriptional regulation, and chromosome arrangements through trans and cis regulation. In this review, focusing on recent advances, we summarize the epigenetic regulatory mechanisms of repetitive sequences in embryonic stem cells. We aim to bridge the knowledge gap by discussing DNA damage repair pathway choices on repetitive sequences and summarizing the significance of chromatin organization on repetitive sequences in response to DNA damage.
View Article and Find Full Text PDFTranslocation renal cell carcinoma (tRCC) is an aggressive subtype of kidney cancer driven by gene fusions, which act via poorly characterized downstream mechanisms. Here we report that TFE3 fusions transcriptionally rewire tRCCs toward oxidative phosphorylation (OXPHOS), contrasting with the highly glycolytic metabolism of most other renal cancers. This TFE3 fusion-driven OXPHOS program, together with heightened glutathione levels found in renal cancers, renders tRCCs sensitive to reductive stress - a metabolic stress state induced by an imbalance of reducing equivalents.
View Article and Find Full Text PDFColorectal cancer (CRC) is characterized by a complex tumor inflammatory microenvironment, while angiogenesis and immunosuppression frequently occur concomitantly. However, the exact mechanism that controls angiogenesis and immunosuppression in CRC microenvironment remains unclear. Herein, we found that expression levels of lipid raft protein STOML2 were increased in CRC and were associated with advanced disease stage and poor survival outcomes.
View Article and Find Full Text PDFPurpose: Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant tumors. Endoplasmic reticulum stress (ERS) plays an essential role in PDAC progression. Here, we aim to identify the ERS-related genes in PDAC and build reliable risk models for diagnosis, prognosis and immunotherapy response of PDAC patients as well as investigate the potential mechanism.
View Article and Find Full Text PDFExtent and efficacy of DNA end resection at DNA double strand break (DSB)s determines the choice of repair pathway. Here we describe how the 53BP1 associated protein DYNLL1 works in tandem with Shieldin and the CST complex to protect DNA ends. DYNLL1 is recruited to DSBs by 53BP1 where it limits end resection by binding and disrupting the MRE11 dimer.
View Article and Find Full Text PDFThe oxidative coupling of imines to ketazine with molecular oxygen is a green process towards the synthesis of hydrazine or hydrazine hydrate, which could efficiently address the economic and environmental issues of the traditional Raschig or peroxide-ketazine process. Herein, we developed an efficient heterogeneous base-free benzophenone imine oxidative coupling route with O catalyzed by Cu/CuO /carbon materials derived from MOFs under mild conditions. Under optimized conditions, the conversion of BI is up to 98.
View Article and Find Full Text PDFCTCF plays key roles in gene regulation, chromatin insulation, imprinting, X chromosome inactivation and organizing the higher-order chromatin architecture of mammalian genomes. Previous studies have mainly focused on the roles of the canonical CTCF isoform. Here, we explore the functions of an alternatively spliced human CTCF isoform in which exons 3 and 4 are skipped, producing a shorter isoform (CTCF-s).
View Article and Find Full Text PDFAliphatic alcohols are common and bulk chemicals in organic synthesis. The site-selective functionalization of non-activated aliphatic alcohols is attractive but challenging. Herein, we report a silver-catalyzed δ-selective Csp-H bond functionalization of abundant and inexpensive aliphatic alcohols.
View Article and Find Full Text PDFPolycomb repressive complex 1 (PRC1) is an important regulator of gene expression and development. PRC1 contains the E3 ligases RING1A/B, which monoubiquitinate lysine 119 at histone H2A (H2AK119ub1), and has been sub-classified into six major complexes based on the presence of a PCGF subunit. Here, we report that PCGF5, one of six PCGF paralogs, is an important requirement in the differentiation of mouse embryonic stem cells (mESCs) towards a neural cell fate.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
September 2017
Compared to the α-functionalization of aldehydes, ketones, even esters, the direct α-modification of amides is still a challenge because of the low acidity of α-CH groups. The α-functionalization of N-H (primary and secondary) amides, containing both an unactived α-C-H bond and a competitively active N-H bond, remains elusive. Shown herein is the general and efficient oxidative α-oxyamination and hydroxylation of aliphatic amides including secondary N-H amides.
View Article and Find Full Text PDFRNA-binding proteins (RBPs), in addition to their functions in cellular homeostasis, play important roles in lineage specification and maintaining cellular identity. Despite their diverse and essential functions, which touch on nearly all aspects of RNA metabolism, the roles of RBPs in somatic cell reprogramming are poorly understood. Here we show that the DEAD-box RBP DDX5 inhibits reprogramming by repressing the expression and function of the non-canonical polycomb complex 1 (PRC1) subunit RYBP.
View Article and Find Full Text PDFA new one-pot cascade reaction of homopropargylic amines with simple imines is developed in the presence of Cu(OTf)2 and affords a series of hexahydro-1H-pyrrolo[3,2-c]quinoline derivatives in good to high yields. This reaction proceeds through an intramolecular hydroamination cyclization of homopropargylic amine to generate a highly reactive dihydropyrrole intermediate in situ. It subsequently reacts with imine via an intermolecular inverse-electron-demand aza-Diels-Alder reaction and a 1,3-H shift to give the fused pyrroloquinoline structures, forming two new C-C bonds and one C-N bond and one N-H bond.
View Article and Find Full Text PDFMutual cooperation in the formal allyl alcohol nucleophilic substitution reaction and hydration of an alkyne has been utilized in the presence of a gold catalyst to give a series of γ-functionalized ketones with high to excellent yields. This reaction actually involved an intramolecular O-H insertion cyclization of an alkyne to form the dihydrofuran intermediate, which was followed by the nucleophilic addition ring-opening of a dihydrofuran to give the target compound.
View Article and Find Full Text PDFNucleosome positioning and histone modification play a critical role in gene regulation, but their role during reprogramming has not been fully elucidated. Here, we determined the genome-wide nucleosome coverage and histone methylation occupancy in mouse embryonic fibroblasts (MEFs), induced pluripotent stem cells (iPSCs) and pre-iPSCs. We found that nucleosome occupancy increases in promoter regions and decreases in intergenic regions in pre-iPSCs, then recovers to an intermediate level in iPSCs.
View Article and Find Full Text PDFOncogenic transcription factors are known to mediate the conversion of somatic cells to tumour or induced pluripotent stem cells (iPSCs). Here we report c-Jun as a barrier for iPSC formation. c-Jun is expressed by and required for the proliferation of mouse embryonic fibroblasts (MEFs), but not mouse embryonic stem cells (mESCs).
View Article and Find Full Text PDFA novel cyclization of 3-acyloxy-1,5-enynes is developed in the presence of PtI2 for the synthesis of substituted unsymmetrical m-terphenyls in good to excellent yields. Two unique steps are involved in this transformation, which includes the elimination of HOAc and benzyl group migration. DFT calculations indicated that the rate-determining step is the migration of the benzylic carbocation to form a zwitterionic intermediate followed by the elimination of HOAc.
View Article and Find Full Text PDFA novel type of transformation was discovered serendipitously during the Barbier-type allenylation reaction of aromatic ketones promoted by the metal, tin, in aqueous media. Additionally, a series of new, highly functionalized 2-bromo-4-aryl-1,3-pentadienes could be obtained with good yields in this reaction. This cascade reaction shows the unique properties of the metal, tin.
View Article and Find Full Text PDFCCCTC-binding factor (CTCF) is a ubiquitously expressed "master weaver" and plays multiple functions in the genome, including transcriptional activation/repression, chromatin insulation, imprinting, X chromosome inactivation, and high-order chromatin organization. It has been shown that CTCF facilitates the recruitment of the upstream binding factor onto ribosomal DNA (rDNA) and regulates the local epigenetic state of rDNA repeats. However, the mechanism by which CTCF modulates rRNA gene transcription has not been well understood.
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