The Hbo1-Brd1/Brpf2 complex is responsible for global acetylation of H3K14 and required for fetal liver erythropoiesis

Mishima, Yumiko; Miyagi, Satoru; Saraya, Atsunori; Negishi, Masamitsu; Endoh, Mitsuhiro; Endo, Takaho A.; Toyoda, Tetsuro; Shinga, Jun; Katsumoto, Takuo; Chiba, Tetsuhiro; Yamaguchi, Naoto; Kitabayashi, Issay; Koseki, Haruhiko; Iwama, Atsushi

doi:10.1182/blood-2011-01-331892

Cited by 175 publications

(241 citation statements)

References 41 publications

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“…Combined with the previous ChIP data, these results provide a promising picture where the interaction between PHD12 and histone H3 helps MOZ promote the HOXA9 promoter acetylation, mainly at the K14 site. Meanwhile, consistent with previous reports (Voss et al 2009;Mishima et al 2011), we found that the global acetylation level remained unperturbed in the absence or presence of cotransfected BRPF1 (Fig. 6B), indicating that the enhancement of the acetylation level might be restricted to specific genes.…”

Section: Phd12 Contributes To the Localization Of Moz On The Hoxa9 Prsupporting

confidence: 93%

Combinatorial readout of unmodified H3R2 and acetylated H3K14 by the tandem PHD finger of MOZ reveals a regulatory mechanism for HOXA9 transcription

Qiu¹,

Liu²,

Zhao³

et al. 2012

Genes Dev.

102

129

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Histone acetylation is a hallmark for gene transcription. As a histone acetyltransferase, MOZ (monocytic leukemia zinc finger protein) is important for HOX gene expression as well as embryo and postnatal development. In vivo, MOZ forms a tetrameric complex with other subunits, including several chromatin-binding modules with regulatory functions. Here we report the solution structure of the tandem PHD (plant homeodomain) finger (PHD12) of human MOZ in a free state and the 1.47 Å crystal structure in complex with H3K14ac peptide, which reveals the structural basis for the recognition of unmodified R2 and acetylated K14 on histone H3. Moreover, the results of chromatin immunoprecipitation (ChIP) and RT-PCR assays indicate that PHD12 facilitates the localization of MOZ onto the promoter locus of the HOXA9 gene, thereby promoting the H3 acetylation around the promoter region and further up-regulating the HOXA9 mRNA level. Taken together, our findings suggest that the combinatorial readout of the H3R2/K14ac by PHD12 might represent an important epigenetic regulatory mechanism that governs transcription and also provide a clue of cross-talk between the MOZ complex and histone H3 modifications.

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Section: Phd12 Contributes To the Localization Of Moz On The Hoxa9 Prsupporting

confidence: 93%

Combinatorial readout of unmodified H3R2 and acetylated H3K14 by the tandem PHD finger of MOZ reveals a regulatory mechanism for HOXA9 transcription

Qiu¹,

Liu²,

Zhao³

et al. 2012

Genes Dev.

102

129

View full text Add to dashboard Cite

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“…Such functionally important tissue-specific variability of paralog subunits in chromatin regulators has been well documented for the BAF(SWI/SNF) remodeling complex (Hargreaves and Crabtree 2011). It is important to point out that HBO1 is nevertheless confirmed as a major mammalian HAT, since its depletion leads to global loss of histone acetylation on H3 in mouse erythroblasts/embryonic fibroblasts or on H4 in HeLa cells (Doyon et al 2006;Kueh et al 2011;Mishima et al 2011). It will be very interesting to determine what is responsible for bulk H4 acetylation in Hbo1 À/À mouse embryonic fibroblasts (Kueh et al 2011).…”

Section: Discussionmentioning

confidence: 94%

“…On the other hand, it was later shown that HBO1 gene knockout in mouse embryos leads instead to a loss of bulk H3K14ac in primary embryonic fibroblasts at embryonic day 9.5 (E9.5), while H4 acetylation persisted (Kueh et al 2011). In addition, a HBO1-BRPF2 complex was reported in K562 leukemic cells and shown to target global H3K14 acetylation and erythroid regulators (Mishima et al 2011). These contradicting results are quite adequately explained in the present study with the finding that HBO1-JADE and HBO1-BRPF HAT complexes coexist within HeLa cells (Fig.…”

Section: Discussionmentioning

confidence: 99%

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Exchange of associated factors directs a switch in HBO1 acetyltransferase histone tail specificity

et al. 2013

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Histone acetyltransferases (HATs) assemble into multisubunit complexes in order to target distinct lysine residues on nucleosomal histones. Here, we characterize native HAT complexes assembled by the BRPF family of scaffold proteins. Their plant homeodomain (PHD)-Zn knuckle-PHD domain is essential for binding chromatin and is restricted to unmethylated H3K4, a specificity that is reversed by the associated ING subunit. Native BRPF1 complexes can contain either MOZ/MORF or HBO1 as catalytic acetyltransferase subunit. Interestingly, while the previously reported HBO1 complexes containing JADE scaffold proteins target histone H4, the HBO1-BRPF1 complex acetylates only H3 in chromatin. We mapped a small region to the N terminus of scaffold proteins responsible for histone tail selection on chromatin. Thus, alternate choice of subunits associated with HBO1 can switch its specificity between H4 and H3 tails. These results uncover a crucial new role for associated proteins within HAT complexes, previously thought to be intrinsic to the catalytic subunit.

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“…However, recent work has shed light on a new mechanism by which some subunits in native modifying complexes can strictly select which specific histone tail gets targeted by the catalytic subunit. We and others have recently discovered that the HBO1 HAT enzyme exists in different native complexes with JADE or BRPF paralogs as scaffold subunit (Doyon et al 2006;Mishima et al 2011;Lalonde et al 2013). While the HBO1-JADE and HBO1-BRPF complexes acetylate H3 and H4 equally on free histones, they are exclusively specific for H4 (JADE) or H3 (BRPF) on chromatin (Lalonde et al 2013).…”

Section: Selection Of the Specific Histone Tail To Be Modified By Enzmentioning

confidence: 99%

Histone target selection within chromatin: an exemplary case of teamwork

2014

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Histone modifiers like acetyltransferases, methyltransferases, and demethylases are critical regulators of most DNA-based nuclear processes, de facto controlling cell cycle progression and cell fate. These enzymes perform very precise post-translational modifications on specific histone residues, which in turn are recognized by different effector modules/proteins. We now have a better understanding of how these enzymes exhibit such specificity. As they often reside in multisubunit complexes, they use associated factors to target their substrates within chromatin structure and select specific histone mark-bearing nucleosomes. In this review, we cover the current understanding of how histone modifiers select their histone targets. We also explain how different experimental approaches can lead to conflicting results about the histone specificity and function of these enzymes.

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The Hbo1-Brd1/Brpf2 complex is responsible for global acetylation of H3K14 and required for fetal liver erythropoiesis

Cited by 175 publications

References 41 publications

Combinatorial readout of unmodified H3R2 and acetylated H3K14 by the tandem PHD finger of MOZ reveals a regulatory mechanism for HOXA9 transcription

Combinatorial readout of unmodified H3R2 and acetylated H3K14 by the tandem PHD finger of MOZ reveals a regulatory mechanism for HOXA9 transcription

Exchange of associated factors directs a switch in HBO1 acetyltransferase histone tail specificity

Histone target selection within chromatin: an exemplary case of teamwork

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