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Structural Basis for Substrate Specificity and Catalysis of Human Histone Acetyltransferase 1

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Structural Basis for Substrate Specificity and Catalysis of Human Histone Acetyltransferase 1 Correction BIOCHEMISTRY Correction for “Structural basis for substrate specificity and ca- talysis of human histone acetyltransferase 1,” by Hong Wu, Natasha Moshkina, Jinrong Min, Hong Zeng, Jennifer Joshua, Ming-Ming Zhou, and Alexander N. Plotnikov, which appeared in issue 23, June 5, 2012, of Proc Natl Acad Sci USA (109:8925– 8930; first published May 21, 2012; 10.1073/pnas.1114117109). The authors note that the review article by M. R. Parthun (ref. 11) provided an excellent summary of the structure and bio- chemical function of HAT1 as a histone acetyltransferase, and served as background introduction for our study. As such, de- scription of some of the specific biochemical functions of HAT1 was not appropriately noted in our article and should be cited and quoted in the following sections: On page 8925, left column, second paragraph, lines 11–15, “In vitro, HAT1 specifically acetylates Lys5 and Lys12 of free (nonnucleosomal) histone H4, and “this specificity is entirely consistent with the pattern of acetylation found on newly syn- thesized histone H4” from many organisms (11).” On page 8925, left column, second paragraph, lines 18–22, “The p46/48 protein “is a WD40 repeat protein” involved in “a wide variety of chromatin-modifying complexes” (11). In yeast, “the association of HAT2 with HAT1 increases the catalytic activity of” HAT1 “by a factor of 10 and appears to function by increasing” HAT1 binding to histone H4 (2, 11).” On page 8925, right column, first full paragraph, lines 8–10, ““Once in the nucleus, the HAT1–HAT2 H3–H4 complex be- comes associated with the histone chaperone/chromatin assem- bly factor HIF1 to form the NuB4 complex” (11).” On page 8930, left column, first full paragraph, lines 1–9, “Because of the important role of HAT1 in chromatin assembly, “a number of studies have begun to link HAT1 to” different types of human cancer (11). “The levels of HAT1” have been found “to increase substantially in liver tumors” (11, 29). Also, “HAT1 mRNA and protein levels are elevated in primary and metastatic human colon cancer tissues” (11, 30). In addition, immunohistochemical studies show that HAT1 is primarily nu- clear in normal cells, but the localization of HAT1 largely shifted to cytoplasm in the tumor tissues (11, 30).” Additionally, Campos, et al. (ref. 12) should be quoted in the following section: On page 8925, right column, first full paragraph, lines 10–16, “In human cells, “the sNASP chaperone binds H3.1–H4 heter- odimers and presents the H4 carboxyl domain to RbAp46,” which “recruits HAT1 activity. After acetylation of histone H4, the complex is stabilized and the histones” are transferred to the ASF1B chaperone. “ASF1B associates with importin-4, and the histones are then transported into the nucleus” (12).” www.pnas.org/cgi/doi/10.1073/pnas.1317790110 CORRECTION www.pnas.org PNAS | November 5, 2013 | vol. 110 | no. 45 | 18339 Downloaded by guest on September 28, 2021 Correction BIOCHEMISTRY Correction for “Structural basis for substrate specificity and ca- talysis of human histone acetyltransferase 1,” by Hong Wu, Natasha Moshkina, Jinrong Min, Hong Zeng, Jennifer Joshua, Ming-Ming Zhou, and Alexander N. Plotnikov, which appeared in issue 23, June 5, 2012, of Proc Natl Acad Sci USA (109:8925– 8930; first published May 21, 2012; 10.1073/pnas.1114117109). Several readers raised allegations of plagiarism concerning the work noted above. The authors note: “The review of this matter was conducted by a subcommittee of the Research Integrity Committee at Icahn School of Medicine at Mount Sinai (New York). The subcommittee did not find that there was plagiarism, but there were findings of inadequate and improper citation of the work of others. Accordingly, we would like to respond and provide corrections to these specific citations as listed below. As this matter was addressed in a previously published correction (1) we will only address newly found issues here. “On page 8925, right column, lines 2–6, the following section should be quoted: ‘combined with specific mutations in the N terminus of histone H3, caused defects in both telomeric gene silencing and resistance to DNA-damaging agents (7–9). Such defects are reproduced by the substitution of Lys for Arg at position 12 of histone H4, but not at position 5,’ and the article by Poveda and Sendra (2) should be cited. “We wish to apologize for any confusion caused by these cita- tions. Please be assured that interpretation of the experiments and the conclusions of this PNAS article are not affected by these clarifications.” 1. Wu H, et al. (2012) Structural basis for substrate specificity and catalysis of human histone acetyltransferase 1. Proc Natl Acad Sci USA 109(23):8925–8930, and correction (2013) 110:18339. 2. Poveda A, Sendra R (2008) Site specificity of yeast histone acetyltransferase B complex in vivo. FEBS J 275:2122–2136. www.pnas.org/cgi/doi/10.1073/pnas.1424013112 E340 | PNAS | January 20, 2015 | vol. 112 | no. 3 www.pnas.org Structural basis for substrate specificity and catalysis of human histone acetyltransferase 1 Hong Wua, Natasha Moshkinab, Jinrong Mina, Hong Zenga, Jennifer Joshuab, Ming-Ming Zhoub, and Alexander N. Plotnikovb,1 aStructural Genomics Consortium, University of Toronto, Toronto, ON, Canada M5G 1L7; and bDepartment of Structural and Chemical Biology, Mount Sinai School of Medicine, New York, NY 10029 Edited by Ronen Marmorstein, The Wistar Institute, Philadelphia, PA, and accepted by the Editorial Board April 19, 2012 (received for review August 29, 2011) Histone acetyltransferase 1 is the founding member of the histone HIF1 alone produced no apparent phenotypic effect (1, 2, 6, 7), acetyltransferase superfamily and catalyzes lysine acetylation of but when combined with specific mutations in the N terminus of newly synthesized histone H4. Here we report a 1.9-Å resolution histone H3, caused defects in both telomeric gene silencing and crystal structure of human histone acetyltransferase 1 in complex resistance to DNA-damaging agents (7–9). Such defects are with acetyl coenzyme A and histone H4 peptide. The crystal struc- reproduced by the substitution of Lys for Arg at position 12 of ture reveals that the cofactor and the side chain of lysine 12 of histone H4, but not at position 5 (8, 9). HAT1 and HAT2 have histone H4 peptide are placed in the canyon between the central been found to interact with the origin recognition complex, and C-terminal domains. Histone H4 peptide adopts a well-defined suggesting a unique role for the HAT1–HAT2 complex at the conformation and establishes an extensive set of interactions with replication fork and likely a role in replication-dependent chro- the enzyme including invariant residues Glu64 and Trp199, which matin assembly (10). together govern substrate-binding specificity of histone acetyltrans- On the basis of the available results, working models have ferase 1. Our structure-guided enzyme kinetic study further demon- emerged to describe the activity of HAT1 in the cell (11, 12). In strates a cumulative effect of the active-site residues Glu187, yeast, the HAT1–HAT2 complex binds to and acetylates newly Glu276, and Asp277 on deprotonation of the ɛ-amino group of synthesized histone H4 in the cytoplasm and remains associated reactive Lys12 for direct attack of the acetyl group of the cofactor. with histone H4. At a certain point, the newly synthesized his- tone H3 joins the complex. The HAT1–HAT2 complex is then istone acetylation is the most prominent posttranslational imported into the nucleus in association with histones H3-H4. Hmodification leading to activation of gene expression, DNA Once in the nucleus, the HAT1–HAT2–H3–H4 complex replication, and DNA repair. It is postulated that histone acet- becomes associated with the histone chaperone/chromatin as- ylation, through charge neutralization of the cationic histone sembly factor HIF1 to form the NuB4 complex. In human cells, tails, weakens nucleosomal electrostatic interactions with anionic the sNASP chaperone binds H3.1–H4 heterodimers and presents DNA, thus destabilizing internucleosomal contacts and nucleo- the H4 carboxyl domain to RbAp46, which recruits HAT1 ac- somal structure and facilitating access to the promoter region for tivity. After acetylation of histone H4, the complex is stabilized RNA polymerase and transcription factors. Histone acetylation and the histones are transferred to the ASF1B chaperone. also plays a functional role in providing binding sites for regu- ASF1B associates with importin-4, and the histones are then latory proteins that mediate transcription and other chromatin- transported into the nucleus (12). These models suggest that based processes. HAT1 may not be functioning exclusively in a catalytic capacity – – Histone acetyltransferase 1 (HAT1; EC 2.3.1.48) is the and that the association of the HAT1 HAT2 (or HAT1 founding member of the family of histone acetyltransferases that RbAp46) complex with histones H4 and H3 may be involved in catalyze the transfer of an acetyl group from acetyl coenzyme A both the import of these histones into the nucleus and their (AcCoA) to the lysine ε-amino groups on the N-terminal tails of subsequent delivery to chromatin assembly factors. BIOCHEMISTRY histones (1, 2). HAT1 has a very broad function in many DNA Despite the fundamental importance of HAT1 in DNA rep- regulatory processes and is found in virtually all eukaryotic lication and chromatin assembly, we still have a limited un- organisms examined (3). Originally, HAT1 was identified as derstanding of its function and regulation as a HAT. The crystal a cytosolic enzyme (2) that acetylates newly synthesized histone structure of yeast HAT1 in complex with AcCoA was reported by H4 molecules before their deposition in replicating chromatin Dutnall et al. (13) who described an overall fold of the enzyme and was therefore suspected of being involved in replication- and its relationship to the structures of other HAT enzymes and dependent chromatin assembly.
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