Rapid and Phosphoinositol-Dependent Binding of the SWI/SNF-like BAF Complex to Chromatin after T Lymphocyte Receptor Signaling

Zhao, Keji; Wang, Weidong; Rando, Oliver J.; Xue, Yutong; Swiderek, Kristine M.; Kuo, Alfred C.; Crabtree, Gerald R.

doi:10.1016/s0092-8674(00)81633-5

Cited by 686 publications

(657 citation statements)

References 40 publications

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“…Signaling pathways that impinge on chromatin remodeling complexes and regulate growth arrest are complex and not completely defined. However, acetylation (27,29,30), phosphorylation (14,20,33,54), and phosphoinositol binding (56) have been shown to affect the ability of several chromatin regulators to form higher-order chromatin domains. Our studies demonstrate that a fraction of total cellular SUV39H1 is specifically phosphorylated during the cell cycle at the G 1 /S transition, an important checkpoint for entry into S phase (41).…”

Section: Discussionmentioning

confidence: 99%

Set Domain-Dependent Regulation of Transcriptional Silencing and Growth Control by SUV39H1, a Mammalian Ortholog of Drosophila Su(var)3-9

Firestein

Cui

Huie

et al. 2000

Molecular and Cellular Biology

101

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Mammalian SET domain-containing proteins define a distinctive class of chromatin-associated factors that are targets for growth control signals and oncogenic activation. SUV39H1, a mammalian ortholog of Drosophila Su(var)3-9, contains both SET and chromo domains, signature motifs for proteins that contribute to epigenetic control of gene expression through effects on the regional organization of chromatin structure. In this report we demonstrate that SUV39H1 represses transcription in a transient transcriptional assay when tethered to DNA through the GAL4 DNA binding domain. Under these conditions, SUV39H1 displays features of a long-range repressor capable of acting over several kilobases to silence basal promoters. A possible role in chromatin-mediated gene silencing is supported by the localization of exogenously expressed SUV39H1 to nuclear bodies with morphologic features suggestive of heterochromatin in interphase cells. In addition, we show that SUV39H1 is phosphorylated specifically at the G 1 /S cell cycle transition and when forcibly expressed suppresses cell growth. Growth suppression as well as the ability of SUV39H1 to form nuclear bodies and silence transcription are antagonized by the oncogenic antiphosphatase Sbf1 that when hyperexpressed interacts with the SET domain and stabilizes the phosphorylated form of SUV39H1. These studies suggest a phosphorylation-dependent mechanism for regulating the chromatin organizing activity of a mammalian su(var) protein and implicate the SET domain as a gatekeeper motif that integrates upstream signaling pathways to epigenetic regulation and growth control.The formation and propagation of higher-order chromatin states are dynamic processes that establish distinct domains that are either permissive or restrictive for transcription. The functions of such domains have been implicated in the epigenetic control of developmental gene expression in Drosophila (38), proper sister chromatid segregation during meiosis (11), and telomeric and centromeric silencing in yeast (22,35). The molecular mechanisms that regulate these and other properties of higher-order chromatin are essentially unknown.Genetic analyses in Drosophila and yeast have identified several genes that participate in the formation of euchromatin or heterochromatin states. Some of these encode proteins that contribute to either an enhancement [E(var)] or suppression [Su(var)] of position effect variegation (PEV) (42). PEV is a gene silencing mechanism that results from the spreading of heterochromatin, thus implicating E(var) and Su(var) proteins in the formation of euchromatic and heterochromatic domains, respectively. Several E(var) and Su(var) proteins share distinctive motifs that are important for their ability to organize chromatin domains. The Su(var)3-9 protein and its mammalian ortholog SUV39H1 are unique in being the only characterized PEV modifiers that share two of these consensus motifs, the chromo and SET domains (1, 50). Chromo domains are 40-amino-acid modular motifs that are implicated in...

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Section: Discussionmentioning

confidence: 99%

Set Domain-Dependent Regulation of Transcriptional Silencing and Growth Control by SUV39H1, a Mammalian Ortholog of Drosophila Su(var)3-9

Firestein

Cui

Huie

et al. 2000

Molecular and Cellular Biology

101

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“…Moreover, a novel mechanism for the regulation of chromatin structure by inositol lipids came with the unexpected discovery that the interaction of the chromatin remodeling complex BAF could be regulated by the level of PtdIns(4,5)P 2 [Zhao et al, 1998]. Resting Tlymphocytes have small, compact nuclei with dense heterochromatin which, upon antigenic stimulation, increase in size with the appearance of euchromatin.…”

Section: Ptdins (45)p 2 and Chromatin Organizationmentioning

confidence: 99%

Nuclear inositol lipid metabolism: More than just second messenger generation?

Martelli

Follo

Evangelisti

et al. 2005

J of Cellular Biochemistry

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A distinct polyphosphoinositide cycle is present in the nucleus, and growing evidence suggests its importance in DNA replication, gene transcription, and apoptosis. Even though it was initially thought that nuclear inositol lipids would function as a source for second messengers, recent findings strongly indicate that lipids present in the nucleus also fulfil other roles. The scope of this review is to highlight the most intriguing advances made in the field over the last few years, such as the possibility that nuclear phosphatidylinositol (4,5) bisphosphate is involved in maintaining chromatin in a transcriptionally active conformation, the new emerging roles for intranuclear phosphatidylinositol (3,4,5) trisphosphate and phosphoinositide 3-kinase, and the evidence which suggests a tight relationship between a decreased level of nuclear phosphoinositide specific phospholipase C-b1 and the evolution of myelodisplastic syndrome into acute myeloid leukemia.

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“…Mouse knockout experiments have also demonstrated that while homozygous loss of INI1 results in early embryonic lethality, heterozygous loss predisposes mice to tumors consistent with MRT (Klochendler-Yeivin et al, 2000;Roberts et al, 2000;Guidi et al, 2001). Finally, actin and actin-related proteins have been found in stoichiometric amounts in hSWI/SNF complexes and are thought to facilitate association with the nuclear matrix (Zhao et al, 1998;Rando et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

“…The chromatin remodeling ability of hSWI/SNF has been shown to respond to various signaling pathways, including response to phosphoinositols (Zhao et al, 1998;Rando et al, 2002), the p38 pathway during skeletal myogenesis (Simone et al, 2004), interferons (Agalioti et al, 2000;Huang et al, 2002;Liu et al, 2002;Cui et al, 2004) and nuclear hormone receptors (Fryer and Archer, 1998;DiRenzo et al, 2000;Belandia et al, 2002;Me´tivier et al, 2003;Link et al, 2005). Phosphatidyl inositol 4,5-bisphosphate (PIP 2 ) has been shown to help increase the association of the SWI/SNF complex with the nuclear matrix (Zhao et al, 1998;Rando et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

“…Phosphatidyl inositol 4,5-bisphosphate (PIP 2 ) has been shown to help increase the association of the SWI/SNF complex with the nuclear matrix (Zhao et al, 1998;Rando et al, 2002). Phosphatidyl inositol 4,5-bisphosphate is also involved in the activation of the serine/ threonine kinase Akt, by recruiting it to the plasma membrane, where it is activated via phosphorylation.…”

Section: Introductionmentioning

confidence: 99%

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Members of the hSWI/SNF chromatin remodeling complex associate with and are phosphorylated by protein kinase B/Akt

et al. 2006

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In an adenosine triphosphate (ATP)-dependent process, the hSWI/SNF chromatin remodeling complex functions to alter chromatin structure, thereby regulating transcription factor access to DNA. In addition to interactions with transcription factors and recognition of acetylated histone residues, the chromatin remodeling activity of hSWI/SNF has also been shown to respond to a variety of cell signaling pathways. Our results demonstrate a novel interaction between the serine/threonine kinase Akt and members of the hSWI/SNF chromatin remodeling complex. Activation of Akt in HeLa cells resulted in its association with hSWI/SNF subunits: INI1, BAF155 and BAF170, as well as actin. BAF155 became preferentially recognized by an antibody that detects phosphorylated Akt substrates upon activation of Akt, suggesting that BAF155 may be an in vivo target for phosphorylation by Akt. Glutathione-S-transferase (GST) pulldown experiments demonstrated that INI1 and BAF155 were both capable of directly interacting with Akt. Finally, in vitro kinase assays provided additional evidence that BAF155 and potentially INI1 are substrates for Akt phosphorylation. These data provide the first evidence that Akt signaling may modulate function of the hSWI/SNF complex.

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Rapid and Phosphoinositol-Dependent Binding of the SWI/SNF-like BAF Complex to Chromatin after T Lymphocyte Receptor Signaling

Cited by 686 publications

References 40 publications

Set Domain-Dependent Regulation of Transcriptional Silencing and Growth Control by SUV39H1, a Mammalian Ortholog of Drosophila Su(var)3-9

Set Domain-Dependent Regulation of Transcriptional Silencing and Growth Control by SUV39H1, a Mammalian Ortholog of Drosophila Su(var)3-9

Nuclear inositol lipid metabolism: More than just second messenger generation?

Members of the hSWI/SNF chromatin remodeling complex associate with and are phosphorylated by protein kinase B/Akt

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