Bivalent interaction of the PZP domain of BRPF1 with the nucleosome impacts chromatin dynamics and acetylation

Klein, Brianna J.; Muthurajan, Uma M.; Lalonde, M.; Gibson, Matthew D.; Andrews, Forest H.; Hepler, Maggie R. D.; Machida, Shuichi; Kou, Yan; Kurumizaka, Hitoshi; Poirier, Michael G.; Côté, Jacques; Luger, Karolin; Kutateladze, Tatiana G.

doi:10.1093/nar/gkv1321

Cited by 49 publications

(74 citation statements)

References 49 publications

(57 reference statements)

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“…601 DNA and NCPs were produced as described in (Klein et al, 2016). Increasing amounts of MORC3 His-ATPase domain (1 to 20 molar excess) were incubated with 601 DNA (3 pM) or with NCPs (3 pM) in 20 mM Tris-HCl pH 7.5 buffer, 150 mM NaCl, 2 mM DTT for 1 hour at room temperature.…”

Section: Methodsmentioning

confidence: 99%

Multivalent Chromatin Engagement and Inter-domain Crosstalk Regulate MORC3 ATPase

Andrews

Tong

Sullivan³

et al. 2016

Cell Reports

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MORC3 is linked to inflammatory myopathies and cancer, however the precise role of MORC3 in normal cell physiology and disease remains poorly understood. Here, we present detailed genetic, biochemical, and structural analyses of MORC3. We demonstrate that MORC3 is significantly upregulated in Down syndrome, and that genetic abnormalities in MORC3 are associated with cancer. The CW domain of MORC3 binds to the methylated histone H3K4 tail, and this interaction is essential for the recruitment of MORC3 to chromatin and accumulation in nuclear bodies. We show that MORC3 possesses intrinsic ATPase activity that requires DNA however is negatively regulated by CW, which interacts with the ATPase domain. Natively linked CW impedes binding of the ATPase domain to DNA, resulting in a decrease in the DNA-stimulated enzymatic activity. Collectively, our studies provide a molecular framework detailing newly identified functions of MORC3 and suggest that its modulation may contribute to human disease.

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Section: Methodsmentioning

confidence: 99%

Multivalent Chromatin Engagement and Inter-domain Crosstalk Regulate MORC3 ATPase

Andrews

Tong

Sullivan³

et al. 2016

Cell Reports

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“…Binding of the BRPF1 PZP domain to nucleosomes facilitates DNA unwrapping and increases DNA accessibility. Moreover, this domain is critical for the HAT function of the MOZ complex toward nucleosomal substrates but is dispensable for that toward free histones (36). Intriguingly, while the ING5 PHD finger binds to H3K4me3, this histone mark was shown to inhibit H3 tail binding by both the MOZ PHD12 finger and the BRPF1/2 PZP domain (30)(31)(32)(33)35).…”

Section: Reader Domains In the Kat6 Complexesmentioning

confidence: 99%

“…As MOZ can acetylate H3K14, the recruitment of MOZ to H3K14ac-enriched regions by its PHD12 finger suggests a mechanism that facilitates the propagation of MOZ-mediated acetylation of H3K14. In addition, the first and second PHD fingers (PZP [PHD-Zn knuckle-PHD] domain) in BRPF1/2 preferentially bind to unmodified H3K4 and DNA, respectively (33)(34)(35)(36). Binding of the BRPF1 PZP domain to nucleosomes facilitates DNA unwrapping and increases DNA accessibility.…”

Section: Reader Domains In the Kat6 Complexesmentioning

confidence: 99%

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

Huang

Abmayr

Workman

2016

Molecular and Cellular Biology

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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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“…9E) (42). Most recently, two structures of the PZP (PHD-Zn-PHD) domain have been reported, in which two PHD domains are connected by a GATA-like finger (43,44). For the BRPF1 PZP domain, the first PHD domain is used to bind unmethylated H3K4 (Fig.…”

Section: Structural Comparison With Other H3k4me3mentioning

confidence: 99%

“…For the BRPF1 PZP domain, the first PHD domain is used to bind unmethylated H3K4 (Fig. 9F) (43), whereas the AF10 PZP domain requires all subdomains to bind a region of histone H3 that spans amino acids 15-34 (44), suggesting that intrinsic varieties are present in these domains. Overall, we propose that the GATA-like finger, CW domain, and PHD domain are basic structure units and that they can be further assembled into the LIM domain, ADD domain, and PZP domain.…”

Section: Structural Comparison With Other H3k4me3mentioning

confidence: 99%

Family-wide Characterization of Histone Binding Abilities of Human CW Domain-containing Proteins

Liu

Tempel

Zhang

et al. 2016

Journal of Biological Chemistry

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Covalent modifications of histone N-terminal tails play a critical role in regulating chromatin structure and controlling gene expression. These modifications are controlled by histone-modifying enzymes and read out by histone-binding proteins. Numerous proteins have been identified as histone modification readers. Here we report the family-wide characterization of histone binding abilities of human CW domain-containing proteins. We demonstrate that the CW domains in ZCWPW2 and MORC3/4 selectively recognize histone H3 trimethylated at Lys-4, similar to ZCWPW1 reported previously, while the MORC1/2 and LSD2 lack histone H3 Lys-4 binding ability. Our crystal structures of the CW domains of ZCWPW2 and MORC3 in complex with the histone H3 trimethylated at Lys-4 peptide reveal the molecular basis of this interaction. In each complex, two tryptophan residues in the CW domain form the "floor" and "right wall," respectively, of the methyllysine recognition cage. Our mutation results based on ZCWPW2 reveal that the right wall tryptophan residue is essential for binding, and the floor tryptophan residue enhances binding affinity. Our structural and mutational analysis highlights the conserved roles of the cage residues of CW domain across the histone methyllysine binders but also suggests why some CW domains lack histone binding ability.Chromatin structure is dynamically regulated by histone post-translational modifications, such as methylation, acetylation, phosphorylation, ubiquitination, and sumoylation (1). These post-translational modifications constitute the "histone code," which is written or erased by histone-modifying enzymes and recognized by histone code "reader" proteins (2-4).Histone methylation, such as lysine methylation at the ⑀-amino group at levels from mono-to trimethylation (me1-me3), has received extensive attention (5). A number of domains bind methylated histone tails. Prominent examples include the chromodomain, Tudor domain, MBT domain, PWWP domain, and PHD domain (4, 6, 7). The CW domain has recently been identified as a new member of the lysine methylation reader family (8 -11).The CW domain is a zinc binding domain, composed of ϳ50 amino acid residues with four conserved cysteine (C) and two conserved tryptophan (W) residues, and its name was derived from these conserved residues. CW domains are found in chromatin-associated proteins in animals and plants and grouped into 12 families based on sequence similarity (12). There are seven CW domain-containing proteins in humans, namely ZCWPW1, ZCWPW2, MORC1, MORC2, MORC3, MORC4, and LSD2 (Fig. 1A). Prior studies have shown that the CW domains of ZCWPW1 (8), MORC3 (10), and MORC4 (9) are readers of H3K4 3 methylated histones with differing preferences for histone H3K4 methylation states (i.e. ZCWPW1 and MORC3 preferentially recognize histone H3K4me3 (8, 10), whereas the CW domain of human MORC4 prefers dimethylated H3K4 (9)). The LSD2 CW domain is required for the demethylation function of LSD2 but does not bind to any H3K4 peptides (13). However, th...

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Bivalent interaction of the PZP domain of BRPF1 with the nucleosome impacts chromatin dynamics and acetylation

Cited by 49 publications

References 49 publications

Multivalent Chromatin Engagement and Inter-domain Crosstalk Regulate MORC3 ATPase

Multivalent Chromatin Engagement and Inter-domain Crosstalk Regulate MORC3 ATPase

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

Family-wide Characterization of Histone Binding Abilities of Human CW Domain-containing Proteins

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