BAF60a Interacts with p53 to Recruit the SWI/SNF Complex

Oh, Jaehak; Sohn, Dong Hyun; Ko, Myunggon; Chung, Hyun Kee; Jeon, Sung Ho; Seong, Rho Hyun

doi:10.1074/jbc.m705401200

Cited by 88 publications

(81 citation statements)

References 45 publications

(53 reference statements)

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“…BAF60a was initially identified as a determinant of the transactivation potential of Fos/Jun dimers to induce the endogenous AP-1-regulated genes such as collagenase and c-met. 32 Its function was further described as a mediator of the antitumor effects of p53, 33 a regulator of hepatic lipid metabolism, 24 and an androgen receptor cofactor that modulates TMPRSS2 expression. 34 This suggests a pleiotropic role of BAF60a in cellular and organismal biology by integrating endocrine, metabolic, and circadian signals.…”

Section: Discussionmentioning

confidence: 99%

SWItch/sucrose nonfermentable (SWI/SNF) complex subunit BAF60a integrates hepatic circadian clock and energy metabolism

et al. 2011

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Many aspects of energy metabolism, including glucose and lipid homeostasis and mitochondrial oxidative metabolism, are under precise control by the mammalian circadian clock. However, the molecular mechanism for coordinate integration of the circadian clock and various metabolic pathways is poorly understood. Here we show that BAF60a, a chromatin-remodeling complex subunit, is rhythmically expressed in the liver of mice. Mice with liver-specific knockdown of BAF60a show abnormalities in the rhythmic expression pattern of clock and metabolic genes and in the circulating metabolite profile. Consistently, knockdown of BAF60a impairs the oscillation of clock genes in serum-shocked HepG 2 cells. At the molecular level, BAF60a activates Bmal1 and G6Pase transcription by way of the coactivation of retinoid-related orphan receptor alpha (RORa). In addition, BAF60a is present near ROR response elements (RORE) on the proximal Bmal1 and G6Pase promoters and turns the chromatin structure into the active state. Conclusion: Our data suggest a critical role for BAF60a in the coordinated regulation of hepatic circadian clock and energy metabolism in mammals. (HEPATOLOGY 2011;54:1410-1420 M any physiological events in mammals, including locomotor activity, sleep, blood pressure, circulating hormones, and energy metabolism show diurnal fluctuation. 1,2 These intrinsic biological rhythms are mainly entrained by light-dark (LD) and feeding cycles. The mammalian master clock resides in the hypothalamic suprachiasmatic nucleus (SCN) and drives slave oscillators distributed in various peripheral tissues through behavioral and neuroendocrine signals. However, Damiola et al. 3 found that peripheral oscillators can be uncoupled and reset from the central pacemaker by restricted feeding. Their findings are supported by the subsequent report showing that restricted feeding entrains the circadian rhythms in peripheral tissues, dominantly in the liver, but leaving SCN rhythms unaffected. 4 Also, both food availability and the temporal pattern of feeding determine the repertoire, phase, and amplitude of the circadian transcriptome in mouse liver. 5 All these studies indicate that nutritional signals play a dominant role in the regulation of peripheral clock function. At the molecular level, Clock and Bmal1 are two basic helix-loop-helix transcription factors that activate the transcription of period (Per) and cryptochrome (Cry) genes. 6 Per and Cry proteins in turn inhibit their own expression by repressing Clock/Bmal1 activity, forming the critical feedback loop within the clock circuitry. In addition, the orphan nuclear receptors of the ROR and Rev-erb families are also implicated in the control of circadian clock function. 7,8 Abbreviations: ChIP, chromatin immunoprecipitation; CO, carbon monoxide; CoIP, coimmunoprecipitation; GFP, green fluorescent protein; GR, glucocorticoid receptor; H3K4me3, trimethylation of lysine 4 of histone 3; H3K9me2, dimethylation of lysine 9 of histone 3; HAT, histone acetyltransferase; HDAC, histone deacetyla...

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Section: Discussionmentioning

confidence: 99%

SWItch/sucrose nonfermentable (SWI/SNF) complex subunit BAF60a integrates hepatic circadian clock and energy metabolism

et al. 2011

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“…Interestingly, Smarcd1/Baf60a mediates the interaction between several signaling pathways and BAF complexes (40). In human cells, a direct interaction between p53 with SMARCD1/BAF60A (but not between p53 and SMARCA4/BRG1) has been reported (41). Uncoupling of the interaction between SMARCD1/ BAF60A and p53 resulted in repression of p53-dependent cellular functions.…”

Section: Discussionmentioning

confidence: 99%

DNA and Chromatin Modification Networks Distinguish Stem Cell Pluripotent Ground States

Song¹,

Saha²,

Gokulrangan³

et al. 2012

Molecular & Cellular Proteomics

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Pluripotent stem cells are capable of differentiating into all cell types of the body and therefore hold tremendous promise for regenerative medicine. Despite their widespread use in laboratories across the world, a detailed understanding of the molecular mechanisms that regulate the pluripotent state is currently lacking. Mouse embryonic (mESC) and epiblast (mEpiSC) stem cells are two closely related classes of pluripotent stem cells, derived from distinct embryonic tissues. Although both mESC and mEpiSC are pluripotent, these cell types show important differences in their properties suggesting distinct pluripotent ground states. To understand the molecular basis of pluripotency, we analyzed the nuclear proteomes of mESCs and mEpiSCs to identify protein networks that regulate their respective pluripotent states. Our study used label-free LC-MS/MS to identify and quantify 1597 proteins in embryonic and epiblast stem cell nuclei. Immunoblotting of a selected protein subset was used to confirm that key components of chromatin regulatory networks are differentially expressed in mESCs and mEpiSCs. Specifically, we identify differential expression of DNA methylation, ATP-dependent chromatin remodeling and nucleosome remodeling networks in mESC and mEpiSC nuclei. This study is the first comparative study of protein networks in cells representing the two distinct, pluripotent states, and points to the importance of DNA and chromatin modification processes in regulating pluripotency. In addition, by integrating our data with existing pluripotency networks, we provide detailed maps of protein networks that regulate pluripotency that will further both the fundamental understanding of pluripotency as well as efforts to reliably control the differentiation of these cells into functional cell fates. Molecular & Cellular Proteomics

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“…The respective BAF60 subunit present in the BAF complex appears to be a commonly employed recruiter via its direct interaction with specific transcription factors (Ito et al 2001;Hsiao et al 2003;Debril et al 2004;Takeuchi et al 2007;Oh et al 2008;Chen et al 2012;Forcales et al 2012;Gallagher et al 2012). Such recruitment is thought to be a prerequisite to enable transcription or to allow access of additional transacting factors (Sudarsanam and Winston 2000).…”

Section: The Ham-3 Paralog Swsn-22 Is An Essential Genementioning

confidence: 99%

The SWI/SNF Chromatin Remodeling Complex Selectively Affects Multiple Aspects of Serotonergic Neuron Differentiation

et al. 2013

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Regulatory programs that control the specification of serotonergic neurons have been investigated by genetic mutant screens in the nematode Caenorhabditis elegans. Loss of a previously uncloned gene, ham-3, affects migration and serotonin antibody staining of the hermaphrodite-specific neuron (HSN) pair. We characterize these defects here in more detail, showing that the defects in serotonin antibody staining are paralleled by a loss of the transcription of all genes involved in serotonin synthesis and transport. This loss is specific to the HSN class as other serotonergic neurons appear to differentiate normally in ham-3 null mutants. Besides failing to migrate appropriately, the HSNs also display axon pathfinding defects in ham-3 mutants. However, the HSNs are still generated and express a subset of their terminal differentiation features in ham-3 null mutants, demonstrating that ham-3 is a specific regulator of select features of the HSNs. We show that ham-3 codes for the C. elegans ortholog of human BAF60, Drosophila Bap60, and yeast Swp73/Rsc6, which are subunits of the yeast SWI/SNF and vertebrate BAF chromatin remodeling complex. We show that the effect of ham-3 on serotonergic fate can be explained by ham-3 regulating the expression of the Spalt/SALL-type Zn finger transcription factor sem-4, a previously identified regulator of serotonin expression in HSNs and of the ham-2 Zn transcription factor, a previously identified regulator of HSN migration and axon outgrowth. Our findings provide the first evidence for the involvement of the BAF complex in the acquisition of terminal neuronal identity and constitute genetic proof by germline knockout that a BAF complex component can have cell-type-specific roles during development. N EURONS that express the neurotransmitter serotonin fulfill a number of critical functions in all nervous systems examined to date. In vertebrates, serotonergic neurons modulate anxiety, cognitive processes, mood, body temperature, sleep, sexual behavior, appetite, and metabolism, and their dysfunction has been connected to a variety of human disorders (Muller and Jacobs 2010). In the hermaphroditic Caenorhabditis elegans nervous system, serotonin also controls a number of distinct behaviors (Schafer 2005;Chase and Koelle 2007). Serotonin is utilized as a neurotransmitter under normal conditions by seven neuron types, the sensory neuron ADF; the interneurons AIM and RIH; the motor neurons hermaphroditespecific neurons (HSNs), the ventral cord motor neurons VC4 and VC5; and the neurosecretory NSM cells (Schafer 2005;Chase and Koelle 2007). Under stress conditions, serotonin is used by an additional neuron type, ASG (Pocock and Hobert 2010). One of the serotonergic neurons, the hermaphrodite-specific motor neuron, HSN, utilizes serotonin to signal to vulval muscles to control egg-laying behavior (Schafer 2005). Unlike most other neurons in the C. elegans nervous system, the two bilaterally symmetric HSNs undergo long-range migration. After terminating migration, they extend th...

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BAF60a Interacts with p53 to Recruit the SWI/SNF Complex

Cited by 88 publications

References 45 publications

SWItch/sucrose nonfermentable (SWI/SNF) complex subunit BAF60a integrates hepatic circadian clock and energy metabolism

SWItch/sucrose nonfermentable (SWI/SNF) complex subunit BAF60a integrates hepatic circadian clock and energy metabolism

DNA and Chromatin Modification Networks Distinguish Stem Cell Pluripotent Ground States

The SWI/SNF Chromatin Remodeling Complex Selectively Affects Multiple Aspects of Serotonergic Neuron Differentiation

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