Regulation of the HAP1 gene involves positive actions of histone deacetylases

Xin, Xiantong; Lan, Changgui; Lee, Hee Chul; Li, Zhang

doi:10.1016/j.bbrc.2007.07.156

Cited by 12 publications

(14 citation statements)

References 30 publications

(61 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is important to note that the constitutive activators bind Hsp82 in cells grown in the absence of inducer, that growth condition in which, by definition, these constitutive activator alleles are active. It is not apparent from our data whether all of the constitutive activator protein is bound to Hsp82 or whether the Hsp82-bound form is capable of DNA binding, as is seen for Hap1p and Hsp70 (Xin et al 2007). …”

Section: Discussionmentioning

confidence: 59%

“…Similarly, hormone releases glucocorticoid receptor from Hsp90 and allows it to enter the nucleus and bind DNA. In the case of Hap1p, Hsp70 but not Hsp90 is reported to bind to Hap1p-dependent promoters along with Hap1p (Xin et al 2007). Thus, the interactions of MAL-activator with the chaperones are similar to those reported for other transcription activator clients but each has unique variations on the common theme.…”

Section: Discussionmentioning

confidence: 72%

“…Hsp70, as opposed to Hsp90, is the negative regulator of Hap1p. Moreover, Hap1p binds DNA while still bound to Hsp70 (Lan et al 2004;Xin et al 2007). When compared with the studies of the glucocorticoid receptor, these findings reveal an unexpected plasticity in the fundamental regulatory roles of the chaperones with regard to these two transcription activators and underscores the importance of extending studies of the Hsp90/Hsp70 chaperone machine to other transcription activator clients in vivo in the native host cell.…”

mentioning

confidence: 98%

See 2 more Smart Citations

Hsp90/Hsp70 Chaperone Machine Regulation of the Saccharomyces MAL-Activator As Determined in Vivo Using Noninducible and Constitutive Mutant Alleles

Ran

Bali²,

Michels

2008

Genetics

View full text Add to dashboard Cite

The Hsp90/Hsp70 chaperone machine is an essential regulator of cell growth and division. It is required for activation of select client proteins, chiefly protein kinases and transcription activators and thus plays a major role in regulating intracellular signaling and gene expression. This report demonstrates, in vivo, the association of the Saccharomyces cerevisiae maltose-responsive transcription activator Mal63 (MAL-activator) with the yeast Hsp70 (Ssa1), Hsp90 (Hsp82), and Hop (Sti1) homologs, using a collection of inducible, constitutive, and noninducible alleles. Each class of mutant activator forms a distinctly different stable multichaperone complex in the absence of maltose. Inducible Mal63p associates with Ssa1, Hsp82, and Sti1 and is released in the presence of maltose. Noninducible mal63 mutant proteins bind to Ssa1 alone and do not stably associate with Hsp82 or Sti1. Constitutive MAL-activators bind well to Hsp82 and poorly to Ssa1 and Sti1, but deletion of STI1 restores Ssa1 binding. Taken together, Mal63p regulation requires the formation of Hsp90/Hsp70 subcomplexes comparable to, yet distinct from those observed with previously characterized Hsp90 clients including glucocorticoid receptor and yeast Hap1p. Thus, comparative studies of different client proteins highlight functional diversity in the operation of the Hsp90/Hsp70 chaperone machine.

show abstract

Section: Discussionmentioning

confidence: 59%

Section: Discussionmentioning

confidence: 72%

mentioning

confidence: 98%

See 1 more Smart Citation

Hsp90/Hsp70 Chaperone Machine Regulation of the Saccharomyces MAL-Activator As Determined in Vivo Using Noninducible and Constitutive Mutant Alleles

Ran

Bali²,

Michels

2008

Genetics

View full text Add to dashboard Cite

show abstract

“…This paradox is unresolved in the literature. At some gene targets, Rpd3L displays the net repressive effect on transcription expected of an HDAC (36)(37)(38), but at others, it has an unexpected net activating effect on transcription (39)(40)(41)(42). In this report, we demonstrate that Rpd3L activates FLO11 transcription via its repressive effects on one of the cis-acting ncRNAs that itself negatively regulates FLO11 transcription.…”

mentioning

confidence: 60%

Toggle involving cis -interfering noncoding RNAs controls variegated gene expression in yeast

Bumgarner

Dowell

Grisafi

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

174

187

View full text Add to dashboard Cite

The identification of specific functional roles for the numerous long noncoding (nc)RNAs found in eukaryotic transcriptomes is currently a matter of intense study amid speculation that these ncRNAs have key regulatory roles. We have identified a pair of cis-interfering ncRNAs in yeast that contribute to the control of variegated gene expression at the FLO11 locus by implementing a regulatory circuit that toggles between two stable states. These capped, polyadenylated ncRNAs are transcribed across the large intergenic region upstream of the FLO11 ORF. As with mammalian long intervening (li)ncRNAs, these yeast ncRNAs (ICR1 and PWR1) are themselves regulated by transcription factors (Sfl1 and Flo8) and chromatin remodelers (Rpd3L) that are key elements in phenotypic transitions in yeast. The mechanism that we describe explains the unanticipated role of a histone deacetylase complex in activating gene expression, because Rpd3L mutants force the ncRNA circuit into a state that silences the expression of the adjacent variegating gene.FLO11 ͉ intergenic transcription ͉ Rpd3L histone deacetylase ͉ transcriptional interference ͉ regulatory RNAs

show abstract

“…These results indicate that SAP18 upregulates MTTP expression by enhancing the binding of mSin3A to these regulatory sequences. Sin3A is usually regarded as transcriptional repressor, but the protein has been shown to activate the transcription of several genes, e.g., Nanog ( 26 ) and HAP ( 27 ). MTTP could be one of those exceptional targets.…”

Section: Discussionmentioning

confidence: 99%

Sin3A-associated protein, 18 kDa, a novel binding partner of TRIB1, regulates MTTP expression [S]

Makishima

Boonvisut

Ishizuka

et al. 2015

Journal of Lipid Research

View full text Add to dashboard Cite

Mammalian tribbles homolog 1 ( TRIB1 ) is a human locus that has been shown to exhibit convincing impact on cardiovascular diseases and plasma lipid concentrations across several ethnic groups. These genetic associations have been demonstrated both in genome-wide SNP association studies ( 1 ) and in subsequent replication studies ( 2 ). In addition, we recently showed the deep association of a TRIB1 regulatory SNP with nonalcoholic fatty liver disease (NAFLD) in individuals of Japanese ancestry ( P = 9.39E-7 ) ( 3 ). Association of TRIB1 SNP with NAFLD was replicated in a Japanese population ( 4 ) and association with plasma alanine aminotransferase (ALT) was reported in a study of individuals of European ancestry ( 5 ), supporting the involvement of TRIB1 in the development of NAFLD. The risk allele of NAFLD decreased transactivation activity ( 3 ). Knockdown of the expression of the mouse homolog ( Trib1 ) in mouse liver increased murine plasma and hepatic lipid levels, whereas Trib1 overexpression decreased these parameters ( 3 ). The enhanced lipogenesis in mouse liver was estimated to result from the reduced protein decay of carbohydrate response element binding protein [ChREBP (MLXIPL)], which is a master regulator for energy storage, coordinating the switch from carbohydrate to lipid via upregulation of glycolysis and lipogenic genes. While the ChREBP knockout mouse is resistant to dietary induced steatosis ( 6 ), ChREBP is not associated with NAFLD in human genetic studies, despite the deep genetic association with plasma TG levels ( 1 ). This observation suggested that an undefi ned pathway might be involved in the pathogenesis of NAFLD associated with TRIB1 .Abstract Mammalian tribbles homolog 1 ( TRIB1 ) is a human locus that has been shown to signifi cantly impact plasma lipid levels across several ethnic groups. In addition, the gene has been associated with the occurrence of nonalcoholic fatty liver disease. In the present study, a yeast-twohybrid system was used to screen for novel molecular targets of TRIB1 binding. Loci corresponding to clones that were positive for TRIB1 binding subsequently were assessed for roles in lipid metabolism in mice using adenoviral constructs to induce knockdown or overexpression. Sin3A-associated protein, 18 kDa (SAP18) was identifi ed as a novel binding partner of TRIB1. Knockdown of the Sap18 in mouse liver decreased plasma lipid levels and increased hepatic lipid levels; SAP18 overexpression showed the opposite effects. Transcriptome analysis of the mouse liver revealed that Sap18 knockdown decreased and SAP18 overexpression increased microsomal TG transfer protein ( MTTP ) expression levels. Chromatin immunoprecipitation analysis showed that halo-tagged SAP18, halo-tagged TRIB1, and anti-mSin3A antibody enriched precipitates for regulatory sequences of the MTTP gene. Enforced expression of SAP18 enhanced and SAP18 knockdown conversely attenuated the enrichment of MTTP regulatory sequences seen with antimSin3A antibody. These studies indicated that SAP18 expressi...

show abstract

Regulation of the HAP1 gene involves positive actions of histone deacetylases

Cited by 12 publications

References 30 publications

Hsp90/Hsp70 Chaperone Machine Regulation of the Saccharomyces MAL-Activator As Determined in Vivo Using Noninducible and Constitutive Mutant Alleles

Hsp90/Hsp70 Chaperone Machine Regulation of the Saccharomyces MAL-Activator As Determined in Vivo Using Noninducible and Constitutive Mutant Alleles

Toggle involving cis -interfering noncoding RNAs controls variegated gene expression in yeast

Sin3A-associated protein, 18 kDa, a novel binding partner of TRIB1, regulates MTTP expression [S]

Contact Info

Product

Resources

About