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Tingchao Mao, Chengquan Han, Ruizhi Deng, Biao Wei, Peng Meng, Yan Luo, Yong Zhang
Epigenetic modifications extensively occur in mammalian embryonic development and cell differentiation process. They play an essential role in the reprogramming of nuclei during somatic cell nuclear transfer (SCNT) and subsequent in vitro embryonic development. Recently, SCNT embryos have been verified to contain a subnormal level of histone H3K4 dimethylation (H3K4me2) in contrast to in vitro fertilized embryos. This finding suggested that increasing H3K4me2 levels may ameliorate the aberrant development of cloned embryos...
March 15, 2018: Systems Biology in Reproductive Medicine
Werner Giehl Glanzner, Vitor Braga Rissi, Mariana Priotto de Macedo, Lady Katerine Serrano Mujica, Karina Gutierrez, Alessandra Bridi, João Ricardo Malheiros de Souza, Paulo Bayard Dias Gonçalves, Vilceu Bordignon
Epigenetic modifications in the C-terminal domain of histones coordinate important events during early development including embryo genome activation (EGA) and cell differentiation. In this study, the mRNA expression profile of the main lysine demethylases (KDMs) acting on the lysine 4 (H3K4), 9 (H3K9) and 27 (H3K27) of the histone H3 was determined at pre-, during and post- EGA stages of bovine and porcine embryos produced by in vitro fertilization (IVF) and somatic cell nuclear transfer (SCNT). In IVF embryos, mRNA abundance of most KDMs revealed a bell-shaped profile with peak expression around the EGA period, i...
March 8, 2018: Biology of Reproduction
Melda Onal, Alex H Carlson, Jeff D Thostenson, Nancy A Benkusky, Mark B Meyer, Seong M Lee, J Wesley Pike
Fibroblast growth factor 23 (FGF23) production is regulated by both calciotropic hormones and inflammation. Consistent with this, elevated FGF23 levels are associated with inflammatory markers as well as parathyroid hormone (PTH) in various disease states, including chronic kidney disease (CKD). However, the molecular mechanisms underpinning Fgf23 transcription in response to these regulators are largely unknown. We therefore utilized chromatin immunoprecipitation followed by DNA sequencing (ChIP-seq) data from an osteocyte cell line to identify potential regulatory regions of the Fgf23 gene...
January 2018: JBMR Plus
Alejandro Saettone, Jyoti Garg, Jean-Philippe Lambert, Syed Nabeel-Shah, Marcelo Ponce, Alyson Burtch, Cristina Thuppu Mudalige, Anne-Claude Gingras, Ronald E Pearlman, Jeffrey Fillingham
BACKGROUND: The chromatin remodelers of the SWI/SNF family are critical transcriptional regulators. Recognition of lysine acetylation through a bromodomain (BRD) component is key to SWI/SNF function; in most eukaryotes, this function is attributed to SNF2/Brg1. RESULTS: Using affinity purification coupled to mass spectrometry (AP-MS) we identified members of a SWI/SNF complex (SWI/SNFTt ) in Tetrahymena thermophila. SWI/SNFTt is composed of 11 proteins, Snf5Tt , Swi1Tt , Swi3Tt , Snf12Tt , Brg1Tt , two proteins with potential chromatin-interacting domains and four proteins without orthologs to SWI/SNF proteins in yeast or mammals...
March 9, 2018: Epigenetics & Chromatin
Nikita I Ershov, Natalya P Bondar, Arina A Lepeshko, Vasiliy V Reshetnikov, Julia A Ryabushkina, Tatiana I Merkulova
BACKGROUND: Maternal separation models in rodents are widely used to establish molecular mechanisms underlying prolonged effects of early life adversity on neurobiological and behavioral outcomes in adulthood. However, global epigenetic signatures following early life stress in these models remain unclear. RESULTS: In this study, we carried out a ChIP-seq analysis of H3K4 trimethylation profile in the prefrontal cortex of adult male mice with a history of early life stress...
February 9, 2018: BMC Genomics
Jaecheol Lee, Ning-Yi Shao, David T Paik, Haodi Wu, Hongchao Guo, Vittavat Termglinchan, Jared M Churko, Youngkyun Kim, Tomoya Kitani, Ming-Tao Zhao, Yue Zhang, Kitchener D Wilson, Ioannis Karakikes, Michael P Snyder, Joseph C Wu
Cardiac development requires coordinated and large-scale rearrangements of the epigenome. The roles and precise mechanisms through which specific epigenetic modifying enzymes control cardiac lineage specification, however, remain unclear. Here we show that the H3K4 methyltransferase SETD7 controls cardiac differentiation by reading H3K36 marks independently of its enzymatic activity. Through chromatin immunoprecipitation sequencing (ChIP-seq), we found that SETD7 targets distinct sets of genes to drive their stage-specific expression during cardiomyocyte differentiation...
March 1, 2018: Cell Stem Cell
Siming Chen, Lianying Jiao, Murtada Shubbar, Xin Yang, Xin Liu
Developmentally regulated accessory subunits dictate PRC2 function. Here, we report the crystal structures of a 120 kDa heterotetrameric complex consisting of Suz12, Rbbp4, Jarid2, and Aebp2 fragments that is minimally active in nucleosome binding and of an inactive binary complex of Suz12 and Rbbp4. Suz12 contains two unique structural platforms that define distinct classes of PRC2 holo complexes for chromatin binding. Aebp2 and Phf19 compete for binding of a non-canonical C2 domain of Suz12; Jarid2 and EPOP occupy an overlapped Suz12 surface required for chromatin association of PRC2...
March 1, 2018: Molecular Cell
Agnieszka Bochyńska, Juliane Lüscher-Firzlaff, Bernhard Lüscher
Regulation of gene expression is achieved by sequence-specific transcriptional regulators, which convey the information that is contained in the sequence of DNA into RNA polymerase activity. This is achieved by the recruitment of transcriptional co-factors. One of the consequences of co-factor recruitment is the control of specific properties of nucleosomes, the basic units of chromatin, and their protein components, the core histones. The main principles are to regulate the position and the characteristics of nucleosomes...
March 2, 2018: Cells
Yanchao Liu, Ying Huang
Chromatin consists of DNA and histones, and specific histone modifications that determine chromatin structure and activity are regulated by three types of proteins, called writer, reader and eraser. Histone reader proteins from vertebrates, vertebrate-infecting parasites, and higher plants possess a CW domain, which has been reported to read histone H3 lysine 4 (H3K4). The CW domain of Arabidopsis SDG8 (also called ASHH2), a histone H3 lysine 36 methyltransferase, preferentially binds monomethylated H3K4 (H3K4me1), unlike the mammalian CW domain protein which binds trimethylated H3K4 (H3K4me3)...
March 1, 2018: Journal of Biological Chemistry
Huimin Qiao, Yanxin Li, Chao Feng, Shuguang Duo, Fen Ji, Jianwei Jiao
The precise function and role of nucleosome assembly protein 1-like 1 (Nap1l1) in brain development are unclear. Here, we find that Nap1l1 knockdown decreases neural progenitor cell (NPC) proliferation and induces premature neuronal differentiation during cortical development. A similar deficiency in embryonic neurogenesis was observed in Nap1l1 knockout (KO) mice, which were generated using the CRISPR-Cas9 system. RNA sequencing (RNA-seq) analysis indicates that Ras-associated domain family member 10 (RassF10) may be the downstream target of Nap1l1...
February 27, 2018: Cell Reports
Yung-Ning Yang, Yu-Tsun Su, Pei-Ling Wu, Chun-Hwa Yang, Yu-Chen S H Yang, Jau-Ling Suen, San-Nan Yang
Bacterial meningitis during the perinatal period may cause long-term neurological deficits. The study investigated whether bacterial lipopolysaccharide (LPS) derived from E. coli. led to neuronal apoptosis with an impaired performance of long-term cognitive function involving the activation of histone modification in the TNF- α gene promoter. Further, we looked into the therapeutic efficacy of granulocyte colony-stimulating factor (G-CSF) in a neonatal brain suffering from perinatal bacterial meningitis. We applied the following research techniques: neurobehavioral tasks, confocal laser microscopy, chromatin immunoprecipitation, and Western blotting...
2018: Oxidative Medicine and Cellular Longevity
Zhiren Zhang, Yanhui Zhai, Xiaoling Ma, Sheng Zhang, Xinglan An, Hao Yu, Ziyi Li
BACKGROUND/AIMS: Aberrantly high levels of H3K4me3, caused by incomplete epigenetic reprogramming, likely cause a low efficiency of somatic cell nuclear transfer (SCNT). Smal molecule inhibitors aimed at epigenetic modification can be used to improve porcine SCNT embryo development. In this study, we examined the effects of MM-102, an H3K4 histone methyltransferase inhibitor, on porcine SCNT preimplantation embryos to investigate the mechanism by which H3K4 methylation regulated global epigenetic reprograming during SCNT...
February 16, 2018: Cellular Physiology and Biochemistry
Xue Bai, Wenjing Bi, Hanyang Dong, Pu Chen, Shanshan Tian, Guijin Zhai, Kai Zhang
Combinatorial histone post-translational modifications (HPTMs) form a complex epigenetic code that can be decoded by specific binding proteins, termed as reader. Their specific interplays have been thought to determine gene expression and downstream biological functions. However, it is still a big challenge to analyze such interaction due to various limitations including rather weak, transient and complicated interactions between HPTMs and readers, the high dynamic property of HPTMs as well as the low abundance of reader proteins...
February 21, 2018: Analytical Chemistry
Yasuto Araki, Yoshimi Aizaki, Kojiro Sato, Hiromi Oda, Riki Kurokawa, Toshihide Mimura
OBJECTIVES: Aberrant histone lysine methylation (HKM) has been reported in rheumatoid arthritis (RA) synovial fibroblasts (SFs). As histone lysine methyltransferases (HKMTs) and demethylases (HKDMs) regulate HKM, these enzymes are believed to be dysregulated in RASFs. The aim of this study is to clarify whether gene expressions of HKMTs and HKDMs are altered in RASFs. METHODS: SFs were isolated from synovial tissues obtained from RA or osteoarthritis (OA) patients during total knee joint replacement...
January 31, 2018: Clinical and Experimental Rheumatology
Shannel R Adams, So Maezawa, Kris G Alavattam, Hironori Abe, Akihiko Sakashita, Megan Shroder, Tyler J Broering, Julie Sroga Rios, Michael A Thomas, Xinhua Lin, Carolyn M Price, Artem Barski, Paul R Andreassen, Satoshi H Namekawa
The sex chromosomes are enriched with germline genes that are activated during the late stages of spermatogenesis. Due to meiotic sex chromosome inactivation (MSCI), these sex chromosome-linked genes must escape silencing for activation in spermatids, thereby ensuring their functions for male reproduction. RNF8, a DNA damage response protein, and SCML2, a germline-specific Polycomb protein, are two major, known regulators of this process. Here, we show that RNF8 and SCML2 cooperate to regulate ubiquitination during meiosis, an early step to establish active histone modifications for subsequent gene activation...
February 20, 2018: PLoS Genetics
Céline Adam, Raphaël Guérois, Anna Citarella, Laura Verardi, Florine Adolphe, Claire Béneut, Vérane Sommermeyer, Claire Ramus, Jérôme Govin, Yohann Couté, Valérie Borde
Histone H3K4 methylation is a feature of meiotic recombination hotspots shared by many organisms including plants and mammals. Meiotic recombination is initiated by programmed double-strand break (DSB) formation that in budding yeast takes place in gene promoters and is promoted by histone H3K4 di/trimethylation. This histone modification is recognized by Spp1, a PHD-finger containing protein that belongs to the conserved histone H3K4 methyltransferase Set1 complex. During meiosis, Spp1 binds H3K4me3 and interacts with a DSB protein, Mer2, to promote DSB formation close to gene promoters...
February 14, 2018: PLoS Genetics
Nam Hoang, Xuan Zhang, Chunxiao Zhang, Van Vo, Feng Leng, Lovely Saxena, Feng Yin, Fei Lu, Guangrong Zheng, Pradip Bhowmik, Hui Zhang
LSD1/KDM1 is a histone demethylase that preferentially removes methyl groups from the mono- and di-methylated lysine 4 in histone H3 (H3K4), key marks for active chromatin for transcriptional activation. LSD1 is essential for pluripotent embryonic stem cells and embryonic teratocarcinoma/carcinoma cells and its expression is often elevated in various cancers. We developed a new LSD1 inhibitor, CBB3001, which potently inhibited LSD1 activity both in vitro and in vivo. CBB3001 also selectively inhibited the growth of human ovarian teratocarcinoma PA-1 and mouse embryonic carcinoma F9 cells, caused the downregulation of pluripotent stem cell proteins SOX2 and OCT4...
February 7, 2018: Bioorganic & Medicinal Chemistry
Jennifer N Dumdie, Kyucheol Cho, Madhuvanthi Ramaiah, David Skarbrevik, Sergio Mora-Castilla, Deborah J Stumpo, Jens Lykke-Andersen, Louise C Laurent, Perry J Blackshear, Miles F Wilkinson, Heidi Cook-Andersen
Global transcriptional silencing is a highly conserved mechanism central to the oocyte-to-embryo transition. We report the unexpected discovery that global transcriptional silencing in oocytes depends on an mRNA decay activator. Oocyte-specific loss of ZFP36L2 an RNA-binding protein that promotes AU-rich element-dependent mRNA decay prevents global transcriptional silencing and causes oocyte maturation and fertilization defects, as well as complete female infertility in the mouse. Single-cell RNA sequencing revealed that ZFP36L2 downregulates mRNAs encoding transcription and chromatin modification regulators, including a large group of mRNAs for histone demethylases targeting H3K4 and H3K9, which we show are bound and degraded by ZFP36L2...
February 5, 2018: Developmental Cell
Kaixiang Cao, Clayton K Collings, Marc A Morgan, Stacy A Marshall, Emily J Rendleman, Patrick A Ozark, Edwin R Smith, Ali Shilatifard
Chromatin regulators control cellular differentiation by orchestrating dynamic developmental gene expression programs, and hence, malfunctions in the regulation of chromatin state contribute to both developmental disorders and disease state. Mll4 (Kmt2d), a member of the COMPASS (COMplex of Proteins ASsociated with Set1) protein family that implements histone H3 lysine 4 monomethylation (H3K4me1) at enhancers, is essential for embryonic development and functions as a pancancer tumor suppressor. We define the roles of Mll4/COMPASS and its catalytic activity in the maintenance and exit of ground-state pluripotency in murine embryonic stem cells (ESCs)...
January 2018: Science Advances
Telmo Henriques, Benjamin S Scruggs, Michiko O Inouye, Ginger W Muse, Lucy H Williams, Adam B Burkholder, Christopher A Lavender, David C Fargo, Karen Adelman
Regulation by gene-distal enhancers is critical for cell type-specific and condition-specific patterns of gene expression. Thus, to understand the basis of gene activity in a given cell type or tissue, we must identify the precise locations of enhancers and functionally characterize their behaviors. Here, we demonstrate that transcription is a nearly universal feature of enhancers in Drosophila and mammalian cells and that nascent RNA sequencing strategies are optimal for identification of both enhancers and superenhancers...
January 1, 2018: Genes & Development
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