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Review
. 2016 Jun 29;36(14):1900-7.
doi: 10.1128/MCB.00055-16. Print 2016 Jul 15.

Regulation of KAT6 Acetyltransferases and Their Roles in Cell Cycle Progression, Stem Cell Maintenance, and Human Disease

Fu Huang  1 , Susan M Abmayr  2 , Jerry L Workman  3
Affiliations
Review

Regulation of KAT6 Acetyltransferases and Their Roles in Cell Cycle Progression, Stem Cell Maintenance, and Human Disease

Fu Huang et al. Mol Cell Biol. .

Abstract

The lysine acetyltransferase 6 (KAT6) histone acetyltransferase (HAT) complexes are highly conserved from yeast to higher organisms. They acetylate histone H3 and other nonhistone substrates and are involved in cell cycle regulation and stem cell maintenance. In addition, the human KAT6 HATs are recurrently mutated in leukemia and solid tumors. Therefore, it is important to understand the mechanisms underlying the regulation of KAT6 HATs and their roles in cell cycle progression. In this minireview, we summarize the identification and analysis of the KAT6 complexes and discuss the regulatory mechanisms governing their enzymatic activities and substrate specificities. We further focus on the roles of KAT6 HATs in regulating cell proliferation and stem cell maintenance and review recent insights that aid in understanding their involvement in human diseases.

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Figures

FIG 1
FIG 1
The KAT6 HAT complexes are evolutionarily conserved. Top, composition of the KAT6 complexes in budding yeast, flies, and mammals, respectively. Homologs in different organisms are marked with the same color. For simplicity, only the NuA3b (NuA3a+Pdp3) complex is shown for budding yeast. Bottom, tables list the domains in complex subunits that recognize histone modifications, with the numbers of domains shown in parentheses. PHD, plant homeodomain; Bromo, bromodomain; PWWP, proline-tryptophan-tryptophan-proline domain.
FIG 2
FIG 2
Functions of KAT6 HATs are regulated by subunits in the complex. Recognition of histone marks by domains in each complex subunit is shown by gray solid lines. Recognition of histone marks predicted according to the structural homology is shown by gray dashed lines. Red lightning marks represent stimulation of enzymatic activity of Enok and MOZ by Br140 and BRPF1, respectively. Red arrows point to acetylation marks added by the KAT6 HATs.
FIG 3
FIG 3
KAT6 HATs are generally involved in cell cycle regulation and stem cell maintenance. Reported interactions and functions are shown by thick solid arrows. Blue double-headed arrows represent genetic interactions between two proteins, red ones represent physical interactions between two proteins, and green ones represent fusions of two proteins. Functional links that are speculated based on published evidence are shown by dotted arrows with question marks. Thin black arrows indicate upregulation (↑) or downregulation (↓) of the indicated process/pathway/protein level. The two subunits of RFC/RFC-like complexes, Rfc1 and Elg1, are shown in yellow. The polycomb complex/protein, PRC1 complex and BMI1, are shown in purple.
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