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chromatin

  • STAT5 Regulation of Sex-Dependent Hepatic CpG Methylation at Distal Regulatory Elements Mapping to Sex-Biased Genes
    Research Article | Spotlight
    STAT5 Regulation of Sex-Dependent Hepatic CpG Methylation at Distal Regulatory Elements Mapping to Sex-Biased Genes

    Growth hormone-activated STAT5b is an essential regulator of sex-differential gene expression in mouse liver; however, its impact on hepatic gene expression and epigenetic responses is poorly understood. Here, we found a substantial, albeit incomplete loss of liver sex bias in hepatocyte-specific STAT5a/STAT5b (collectively, STAT5)-deficient mouse liver.

    Pengying Hao, David J. Waxman
  • Mutual Balance of Histone Deacetylases 1 and 2 and the Acetyl Reader ATAD2 Regulates the Level of Acetylation of Histone H4 on Nascent Chromatin of Human Cells
    Research Article | Spotlight
    Mutual Balance of Histone Deacetylases 1 and 2 and the Acetyl Reader ATAD2 Regulates the Level of Acetylation of Histone H4 on Nascent Chromatin of Human Cells

    Newly synthesized histone H4 that is incorporated into chromatin during DNA replication is acetylated on lysines 5 and 12. Histone deacetylase 1 (HDAC1) and HDAC2 are responsible for reducing H4 acetylation as chromatin matures. Using CRISPR-Cas9-generated hdac1- or hdac2-null fibroblasts, we determined that HDAC1 and HDAC2 do not fully compensate for each other in removing de novo acetyls on H4 in vivo...

    Pavlo Lazarchuk, John Hernandez-Villanueva, Maria N. Pavlova, Alexander Federation, Michael MacCoss, Julia M. Sidorova
  • HBO1 (KAT7) Does Not Have an Essential Role in Cell Proliferation, DNA Replication, or Histone 4 Acetylation in Human Cells
    Research Article
    HBO1 (KAT7) Does Not Have an Essential Role in Cell Proliferation, DNA Replication, or Histone 4 Acetylation in Human Cells

    HBO1 (MYST2/KAT7) is essential for histone 3 lysine 14 acetylation (H3K14ac) but is dispensable for H4 acetylation and DNA replication in mouse tissues. In contrast, previous studies using small interfering RNA (siRNA) knockdown in human cell lines have suggested that HBO1 is essential for DNA replication. To determine if HBO1 has distinctly different roles in immortalized human cell lines and normal mouse cells, we performed siRNA...

    Andrew J. Kueh, Samantha Eccles, Leonie Tang, Alexandra L. Garnham, Rose E. May, Marco J. Herold, Gordon K. Smyth, Anne K. Voss, Tim Thomas
  • Function of the MYND Domain and C-Terminal Region in Regulating the Subcellular Localization and Catalytic Activity of the SMYD Family Lysine Methyltransferase Set5
    Research Article
    Function of the MYND Domain and C-Terminal Region in Regulating the Subcellular Localization and Catalytic Activity of the SMYD Family Lysine Methyltransferase Set5

    SMYD lysine methyltransferases target histones and nonhistone proteins for methylation and are critical regulators of muscle development and implicated in neoplastic transformation. They are characterized by a split catalytic SET domain and an intervening MYND zinc finger domain, as well as an extended C-terminal domain. Saccharomyces cerevisiae contains two SMYD...

    Deepika Jaiswal, Rashi Turniansky, James J. Moresco, Sabeen Ikram, Ganesh Ramaprasad, Assefa Akinwole, Julie Wolf, John R. Yates, Erin M. Green
  • Open Access
    MacroH2A1 Regulation of Poly(ADP-Ribose) Synthesis and Stability Prevents Necrosis and Promotes DNA Repair
    Research Article
    MacroH2A1 Regulation of Poly(ADP-Ribose) Synthesis and Stability Prevents Necrosis and Promotes DNA Repair

    Through its ability to bind the ends of poly(ADP-ribose) (PAR) chains, the function of the histone variant macroH2A1.1, including its ability to regulate transcription, is coupled to PAR polymerases (PARPs). PARP1 also has a major role in DNA damage response (DDR) signaling, and our results show that macroH2A1 alters the kinetics of PAR accumulation following acute DNA damage by both suppressing PARP activity and simultaneously...

    Penelope D. Ruiz, Gregory A. Hamilton, Jong Woo Park, Matthew J. Gamble
  • Regional Gene Repression by DNA Double-Strand Breaks in G<sub>1</sub> Phase Cells
    Research Article
    Regional Gene Repression by DNA Double-Strand Breaks in G1 Phase Cells

    DNA damage responses (DDR) to double-strand breaks (DSBs) alter cellular transcription programs at the genome-wide level. Through processes that are less well understood, DSBs also alter transcriptional responses locally, which may be important for efficient DSB repair. Here, we developed an approach to elucidate the cis-acting responses to DSBs in G1 phase cells.

    Caitlin E. Purman, Patrick L. Collins, Sofia I. Porter, Ankita Saini, Harshath Gupta, Barry P. Sleckman, Eugene M. Oltz
  • FANCD2 Binding to H4K20me2 via a Methyl-Binding Domain Is Essential for Efficient DNA Cross-Link Repair
    Research Article
    FANCD2 Binding to H4K20me2 via a Methyl-Binding Domain Is Essential for Efficient DNA Cross-Link Repair

    Fanconi anemia (FA) is an inherited disease characterized by bone marrow failure and increased cancer risk. FA is caused by mutation of any 1 of 22 genes, and the FA proteins function cooperatively to repair DNA interstrand cross-links (ICLs). A central step in the activation of the FA pathway is the monoubiquitination of the FANCD2 and FANCI proteins, which occurs within chromatin. How FANCD2 and FANCI are anchored to chromatin remains...

    Karissa L. Paquin, Nicholas E. Mamrak, Jada L. Garzon, Juan A. Cantres-Velez, Paul A. Azzinaro, Elizabeth A. Vuono, Kevin E. Lima, Jodi L. Camberg, Niall G. Howlett
  • Open Access
    tRNA Genes Affect Chromosome Structure and Function via Local Effects
    Research Article
    tRNA Genes Affect Chromosome Structure and Function via Local Effects

    The genome is packaged and organized in an ordered, nonrandom manner, and specific chromatin segments contact nuclear substructures to mediate this organization. tRNA genes (tDNAs) are binding sites for transcription factors and architectural proteins and are thought to play an important role in the organization of the genome.

    Omar Hamdani, Namrita Dhillon, Tsung-Han S. Hsieh, Takahiro Fujita, Josefina Ocampo, Jacob G. Kirkland, Josh Lawrimore, Tetsuya J. Kobayashi, Brandon Friedman, Derek Fulton, Kenneth Y. Wu, Răzvan V. Chereji, Masaya Oki, Kerry Bloom, David J. Clark, Oliver J. Rando, Rohinton T. Kamakaka
  • Open Access
    Rapid Recapitulation of Nonalcoholic Steatohepatitis upon Loss of Host Cell Factor 1 Function in Mouse Hepatocytes
    Research Article | Spotlight
    Rapid Recapitulation of Nonalcoholic Steatohepatitis upon Loss of Host Cell Factor 1 Function in Mouse Hepatocytes

    Host cell factor 1 (HCF-1), encoded by the ubiquitously expressed X-linked gene Hcfc1, is an epigenetic coregulator important for mouse development and cell proliferation, including during liver regeneration. We used a hepatocyte-specific inducible Hcfc1 knockout allele (called Hcfc1hepKO) to induce HCF-1 loss in hepatocytes of hemizygous Hcfc1hepKO/Y males by 4 days.

    ...
    Shilpi Minocha, Dominic Villeneuve, Viviane Praz, Catherine Moret, Maykel Lopes, Danièle Pinatel, Leonor Rib, Nicolas Guex, Winship Herr
  • Open Access
    Research Article | Spotlight
    Identification of a Novel Enhancer/Chromatin Opening Element Associated with High-Level γ-Globin Gene Expression

    The organization of the five β-type globin genes on chromosome 11 reflects the timing of expression during erythroid cell development, with the embryonic ε-globin gene being located at the 5′ end, followed by the two fetal γ-globin genes, and with the adult β- and δ-globin genes being located at the 3′ end. Here, we functionally characterized a DNase I-hypersensitive site (HS) located 4 kb upstream of the Gγ-globin gene (HBG-4kb HS)....

    Yong Shen, MacLean A. Bassett, Aishwarya Gurumurthy, Rukiye Nar, Isaac J. Knudson, Cameron R. Guy, Alex Perez, Russell W. Mellen, Masatoshi Ikeda, Mir A. Hossain, Suming Huang, Kazuhiko Igarashi, Jörg Bungert

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