ATAC is a double histone acetyltransferase complex that stimulates nucleosome sliding

Suganuma, Tamaki; Gutiérrez, José L.; Li, Bing; Florens, Laurence; Swanson, Selene K.; Washburn, Michael P.; Abmayr, Susan M.; Workman, Jerry L.

doi:10.1038/nsmb.1397

Cited by 183 publications

(212 citation statements)

References 58 publications

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“…Moreover, Herring and co-workers (48) reported that CHD8 interacted with SRF and modulated the function of SRF-dependent SMC-marker genes. Of interest, we report herein that WDR5 is contained within human ATAC2 histone acetyltransferase complexes, results consistent with two previous reports (34,35). However, the function of WDR5 within these complexes is unknown.…”

Section: Evidence That Wdr5 Mediates Chromatin Remodeling and Transcrsupporting

confidence: 80%

“…Of interest, ATAC2 is the binding protein for CRP2 that has previously been shown to induce expression of multiple SMC-marker genes in fibroblast cells in combination with GATA4 and SRF (32,33). ATAC2 belongs to a histone acetyltransferase complex and has histone deacetylase activity by itself (34,35). Consistent with our findings, two different groups provided evidence that WDR5 is contained within the ATAC2 complex within several different cell types (34,35).…”

Section: Wdr5 Forms a Multiprotein Complex With H3k4 Hkmt Activity Ansupporting

confidence: 76%

“…ATAC2 belongs to a histone acetyltransferase complex and has histone deacetylase activity by itself (34,35). Consistent with our findings, two different groups provided evidence that WDR5 is contained within the ATAC2 complex within several different cell types (34,35). Of great interest, Ash2L, one of the subunits within the core of WDR5-RbBP5-Ash2L, appeared in the WDR5 complex in RA-treated A404 cells but not in the undifferentiated cells.…”

Section: Wdr5 Forms a Multiprotein Complex With H3k4 Hkmt Activity Ansupporting

confidence: 74%

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WD Repeat-containing Protein 5, a Ubiquitously Expressed Histone Methyltransferase Adaptor Protein, Regulates Smooth Muscle Cell-selective Gene Activation through Interaction with Pituitary Homeobox 2

Gan¹,

Thiébaud²,

Thézé³

et al. 2011

Journal of Biological Chemistry

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WD repeat-containing protein 5 (WDR5) is a common component of mammalian mixed lineage leukemia methyltransferase family members and is important for histone H3 lysine 4 methylation (H3K4me), which has been implicated in control of activation of cell lineage genes during embryogenesis. However, WDR5 has not been considered to play a specific regulatory role in epigenetic programming of cell lineage because it is ubiquitously expressed. Previous work from our laboratory showed the appearance of histone H3K4me within smooth muscle cell (SMC)-marker gene promoters during the early stages of development of SMC from multipotential embryonic cells but did not elucidate the underlying mechanisms that mediate SMC-specific and locus-selective H3K4me. Results presented herein show that knockdown of WDR5 significantly decreased SMCmarker gene expression in cultured SMC differentiation systems and in Xenopus laevis embryos in vivo. In addition, we showed that WDR5 complexes within SMC progenitor cells contained H3K4 methyltransferase enzymatic activity and that knockdown of WDR5 selectively decreased H3K4me1 and H3K4me3 enrichment within SMC-marker gene promoter loci. Moreover, we present evidence that it is recruited to these gene promoter loci through interaction with a SMC-selective pituitary homeobox 2 (Pitx2). Taken together, studies provide evidence for a novel mechanism for epigenetic control of SMCmarker gene expression during development through interaction of WDR5, homeodomain proteins, and chromatin remodeling enzymes.A critical question in developmental biology is how cell lineage-specific gene expression patterns are established and propagated during embryogenesis. Although the exact mechanisms by which complex patterns of gene expression are established during development are unclear, epigenetic modification of chromatin appears to play an important role in the transition of embryonic stem cells (ESCs) 2 into committed cell lineages (1, 2). Among the epigenetic modifications, histone methylation is an important primary determinant of cellular identity. In pluripotent ESCs, many lineage-specific genes are labeled with a unique bivalent histone modification pattern consisting of "activating" histone H3 lysine 4 methylation (H3K4me) and "repressive" H3 lysine 27 methylation (H3K27me) modifications. During the process of lineage determination from ESCs, these "bivalent domains" are resolved into constitutive H3K4me loci within genes that are actively expressed or H3K27me loci within genes that are repressed in specific cell lineages (2-4). In mammalian cells, H3K4me is mainly carried out by the mixed lineage leukemia (MLL) family members and SET1A/SET1B (5-7). These MLL/SET members have H3K4 methyltransferase (HKMT) activity through a conserved SET domain and form a complex with conserved subunits WDR5, Ash2L, and RbBP5 (8, 9). WDR5 is required to keep the MLL/ SET associated with the rest of the complex and is required for its activity (10). Although WDR5 was previously shown to be an H3K4me-binding protein impor...

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Section: Evidence That Wdr5 Mediates Chromatin Remodeling and Transcrsupporting

confidence: 80%

Section: Wdr5 Forms a Multiprotein Complex With H3k4 Hkmt Activity Ansupporting

confidence: 76%

Section: Wdr5 Forms a Multiprotein Complex With H3k4 Hkmt Activity Ansupporting

confidence: 74%

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WD Repeat-containing Protein 5, a Ubiquitously Expressed Histone Methyltransferase Adaptor Protein, Regulates Smooth Muscle Cell-selective Gene Activation through Interaction with Pituitary Homeobox 2

Gan¹,

Thiébaud²,

Thézé³

et al. 2011

Journal of Biological Chemistry

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“…The WDR5 protein is a subunit not only of the NSL complex but also of the MLL/SET1-containing histone H3K4 methyltransferase complexes (34) and of the ATAC (ADA2-containing) HAT complex, which includes as catalytic subunits both the GCN5/KAT2 and the ATAC2/KAT14 HATs (35,36). The degree to which the presence of these shared subunits argues for functional links between the NSL, INO80, ATAC, and MLL/SET1-containing histone H3K4 methyltransferase complexes remains to be determined.…”

Section: Discussionmentioning

confidence: 99%

Subunit Composition and Substrate Specificity of a MOF-containing Histone Acetyltransferase Distinct from the Male-specific Lethal (MSL) Complex

Cai

Jin

Swanson

et al. 2010

Journal of Biological Chemistry

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236

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Here we report an analysis of the subunit composition and substrate specificity of the NSL complex. Proteomic analyses of complexes purified through multiple candidate subunits reveal that NSL is composed of nine subunits. Two of its subunits, WD repeat domain 5 (WDR5) and host cell factor 1 (HCF1), are shared with members of the MLL/SET family of histone H3 lysine 4 (H3K4) methyltransferase complexes, and a third subunit, MCRS1, is shared with the human INO80 chromatin-remodeling complex. In addition, we show that assembly of the MOF HAT into MSL or NSL complexes controls its substrate specificity. Although MSL-associated MOF acetylates nucleosomal histone H4 almost exclusively on lysine 16, NSLassociated MOF exhibits a relaxed specificity and also acetylates nucleosomal histone H4 on lysines 5 and 8.In eukaryotic cells, chromosomal DNA is packaged with histones and other proteins into chromatin. Alterations in chromatin structure affect the accessibility of chromosomal DNA to enzymes involved in transcription, replication, and repair. Changes in chromatin structure are regulated in at least three different ways: by ATP-dependent remodeling of nucleosomes, by the incorporation of variants of histones H2A and H3 into nucleosomes, and by post-translational modifications of histones (1-5).Post-translational modifications of histones include acetylation, methylation, phosphorylation, ubiquitination, sumoylation, and ADP-ribosylation (4 -6). Reversible histone acetylation, controlled by histone acetyltransferases (HATs) 4 and histone deacetylases, plays an important role in regulation of chromatin structure and function (3, 7). Based on the nature of their catalytic domains, HATs can be grouped into two distinct families: the GCN5-related N-acetyltransferase (GNAT) family, which includes GCN5 and p300/CBP-associating factor (8), and the Moz-Ybf2/Sas3-Sas2-Tip60 (MYST) family, which is characterized by a highly conserved MYST domain composed of an acetyl-CoA binding motif and a zinc finger (9, 10). Some MYST family members also have additional structural features such as chromodomains (MOF, Esa1, and Tip60), plant homeodomain-linked zinc fingers (Moz and MORF), and other domains that bind specifically to modified histones or participate in other protein-protein interactions (10).Human MOF is an ortholog of the Drosophila MOF HAT. MOF is one of the key components of the dosage compensation or male-specific lethal (MSL) complex. The Drosophila MSL complex is composed of at least five proteins (MSL1, MSL2, MSL3, MLE, and MOF) and two non-coding RNAs (roX1 and roX2). Human cells express an evolutionarily conserved MSL complex that is composed of MOF and at least three additional subunits, including orthologs of MSL1, MSL2, and MSL3. The MOF HAT is believed to be responsible for the majority of histone H4 acetylation at lysine 16 in both Drosophila and human cells (4,(11)(12)(13).Results of recent studies suggest the existence of additional MOF-containing HAT complexes. Roeder and co-workers (14) reported that in addition...

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“…Moreover, some of these complexes also possess more than one activity. For example, the SAGA complex has both acetyltransferase (Gcn5) and deubiquitinase (Ubp8) activities (Ingvarsdottir et al 2005;Lee et al 2005), while the related ATAC complex possesses two acetyltransferases (Gcn5 and Atac2) (Suganuma et al 2008). Other complexes, such as TIP60, combine chromatin remodeling (H2A.Z incorporation by the p400 subunit) and modifying activities (acetylation by the Tip60 subunit) (Kusch et al 2004;Altaf et al 2009).…”

mentioning

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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ATAC is a double histone acetyltransferase complex that stimulates nucleosome sliding

Cited by 183 publications

References 58 publications

WD Repeat-containing Protein 5, a Ubiquitously Expressed Histone Methyltransferase Adaptor Protein, Regulates Smooth Muscle Cell-selective Gene Activation through Interaction with Pituitary Homeobox 2

WD Repeat-containing Protein 5, a Ubiquitously Expressed Histone Methyltransferase Adaptor Protein, Regulates Smooth Muscle Cell-selective Gene Activation through Interaction with Pituitary Homeobox 2

Subunit Composition and Substrate Specificity of a MOF-containing Histone Acetyltransferase Distinct from the Male-specific Lethal (MSL) Complex

Histone target selection within chromatin: an exemplary case of teamwork

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