Histone acetyltransferase KAT7

Definition:

Catalytic subunit of histone acetyltransferase HBO1 complexes, which specifically mediate acetylation of histone H3 at 'Lys-14' (H3K14ac), thereby regulating various processes, such as gene transcription, protein ubiquitination, immune regulation, stem cell pluripotent and self-renewal maintenance and embryonic development. Some complexes also catalyze acetylation of histone H4 at 'Lys-5', 'Lys-8' and 'Lys-12' (H4K5ac, H4K8ac and H4K12ac, respectively), regulating DNA replication initiation, regulating DNA replication initiation. Specificity of the HBO1 complexes is determined by the scaffold subunit: complexes containing BRPF scaffold (BRPF1, BRD1/BRPF2 or BRPF3) direct KAT7/HBO1 specificity towards H3K14ac, while complexes containing JADE (JADE1, JADE2 and JADE3) scaffold direct KAT7/HBO1 specificity towards histone H4. H3K14ac promotes transcriptional elongation by facilitating the processivity of RNA polymerase II. Acts as a key regulator of hematopoiesis by forming a complex with BRD1/BRPF2, directing KAT7/HBO1 specificity towards H3K14ac and promoting erythroid differentiation. H3K14ac is also required for T-cell development (By similarity). KAT7/HBO1-mediated acetylation facilitates two consecutive steps, licensing and activation, in DNA replication initiation: H3K14ac facilitates the activation of replication origins, and histone H4 acetylation (H4K5ac, H4K8ac and H4K12ac) facilitates chromatin loading of MCM complexes, promoting DNA replication licensing. Acts as a positive regulator of centromeric CENPA assembly: recruited to centromeres and mediates histone acetylation, thereby preventing centromere inactivation mediated by SUV39H1, possibly by increasing histone turnover/exchange. Involved in nucleotide excision repair: phosphorylation by ATR in response to ultraviolet irradiation promotes its localization to DNA damage sites, where it mediates histone acetylation to facilitate recruitment of XPC at the damaged DNA sites. Acts as an inhibitor of NF-kappa-B independently of its histone acetyltransferase activity.; Plays a central role in the maintenance of leukemia stem cells in acute myeloid leukemia (AML). Acts by mediating acetylation of histone H3 at 'Lys-14' (H3K14ac), thereby facilitating the processivity of RNA polymerase II to maintain the high expression of key genes, such as HOXA9 and HOXA10 that help to sustain the functional properties of leukemia stem cells.

References:

[1]. Laura MacPherson, et al. HBO1 is required for the maintenance of leukaemia stem cells. Nature. 2020 Jan;577(7789):266-270. [Content Brief]

[2]. Yunpeng Feng, et al. BRPF3-HBO1 regulates replication origin activation and histone H3K14 acetylation. EMBO J. 2016 Jan 18;35(2):176-92. [Content Brief]

[3]. Benoit Miotto, et al. HBO1 histone acetylase is a coactivator of the replication licensing factor Cdt1. Genes Dev. 2008 Oct 1;22(19):2633-8. [Content Brief]

[4]. Hiroyuki Niida, et al. Phosphorylated HBO1 at UV irradiated sites is essential for nucleotide excision repair. Nat Commun. 2017 Jul 18;8:16102. [Content Brief]

[5]. T W Burke, et al. Replication factors MCM2 and ORC1 interact with the histone acetyltransferase HBO1. J Biol Chem. 2001 May 4;276(18):15397-408. [Content Brief]

[6]. M Iizuka, et al. Histone acetyltransferase HBO1 interacts with the ORC1 subunit of the human initiator protein. J Biol Chem. 1999 Aug 13;274(33):23027-34. [Content Brief]

[7]. Benoit Miotto, et al. HBO1 histone acetylase activity is essential for DNA replication licensing and inhibited by Geminin. Mol Cell. 2010 Jan 15;37(1):57-66. [Content Brief]

[8]. Marie-Eve Lalonde, et al. Exchange of associated factors directs a switch in HBO1 acetyltransferase histone tail specificity. Genes Dev. 2013 Sep 15;27(18):2009-24. [Content Brief]

[9]. Romuald Contzler, et al. Histone acetyltransferase HBO1 inhibits NF-kappaB activity by coactivator sequestration. Biochem Biophys Res Commun. 2006 Nov 10;350(1):208-13. [Content Brief]

[10]. Jun-Ichirou Ohzeki, et al. KAT7/HBO1/MYST2 Regulates CENP-A Chromatin Assembly by Antagonizing Suv39h1-Mediated Centromere Inactivation. Dev Cell. 2016 Jun 6;37(5):413-27. [Content Brief]

[11]. Yuta Mishima, et al. The Hbo1-Brd1/Brpf2 complex is responsible for global acetylation of H3K14 and required for fetal liver erythropoiesis. Blood. 2011 Sep 1;118(9):2443-53. [Content Brief]

[12]. Yannick Doyon, et al. ING tumor suppressor proteins are critical regulators of chromatin acetylation required for genome expression and perpetuation. Mol Cell. 2006 Jan 6;21(1):51-64. [Content Brief]

[13]. Nehmé Saksouk, et al. HBO1 HAT complexes target chromatin throughout gene coding regions via multiple PHD finger interactions with histone H3 tail. Mol Cell. 2009 Jan 30;33(2):257-65. [Content Brief]

[14]. Benoit Miotto, et al. JNK1 phosphorylation of Cdt1 inhibits recruitment of HBO1 histone acetylase and blocks replication licensing in response to stress. Mol Cell. 2011 Oct 7;44(1):62-71. [Content Brief]

[15]. Andrew J Kueh, et al. HBO1 (KAT7) Does Not Have an Essential Role in Cell Proliferation, DNA Replication, or Histone 4 Acetylation in Human Cells. Mol Cell Biol. 2020 Jan 30;40(4):e00506-19. [Content Brief]

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