scholarly journals The histone acetyltransferase PCAF regulates p21 transcription through stress-induced acetylation of histone H3

Cell Cycle ◽  
2012 ◽  
Vol 11 (13) ◽  
pp. 2458-2466 ◽  
Author(s):  
Ian M. Love ◽  
Pedja Sekaric ◽  
Dingding Shi ◽  
Steven R. Grossman ◽  
Elliot J. Androphy
Keyword(s):  
Histone Acetyltransferase ◽  
Histone H3

scholarly journals Nuclear condensates of p300 formed though the structured catalytic core can act as a storage pool of p300 with reduced HAT activity

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yi Zhang ◽  
Kyle Brown ◽  
Yucong Yu ◽  
Ziad Ibrahim ◽  
Mohamad Zandian ◽  
...  
Keyword(s):  
Phase Separation ◽  
Cell Nucleus ◽  
Active Site ◽  
Histone Acetyltransferase ◽  
Histone H3 ◽  
Catalytic Core ◽  
Cellular Processes ◽  
Storage Pool ◽  
Core Components ◽  
Acetyltransferase P300

AbstractThe transcriptional co-activator and acetyltransferase p300 is required for fundamental cellular processes, including differentiation and growth. Here, we report that p300 forms phase separated condensates in the cell nucleus. The phase separation ability of p300 is regulated by autoacetylation and relies on its catalytic core components, including the histone acetyltransferase (HAT) domain, the autoinhibition loop, and bromodomain. p300 condensates sequester chromatin components, such as histone H3 tail and DNA, and are amplified through binding of p300 to the nucleosome. The catalytic HAT activity of p300 is decreased due to occlusion of the active site in the phase separated droplets, a large portion of which co-localizes with chromatin regions enriched in H3K27me3. Our findings suggest a model in which p300 condensates can act as a storage pool of the protein with reduced HAT activity, allowing p300 to be compartmentalized and concentrated at poised or repressed chromatin regions.

scholarly journals Interplay between Chromatin and trans-Acting Factors on the IME2 Promoter upon Induction of the Gene at the Onset of Meiosis

2006 ◽  
Vol 27 (4) ◽  
pp. 1254-1263 ◽  
Author(s):  
Tomomi Inai ◽  
Masashi Yukawa ◽  
Eiko Tsuchiya
Keyword(s):  
Histone Deacetylase ◽  
Chromatin Structure ◽  
Molecular Basis ◽  
Histone Acetyltransferase ◽  
Histone H3 ◽  
Repressive Chromatin ◽  
Tata Element ◽  
Histone H3 Acetylation ◽  
Low Levels ◽  
H3 Acetylation

ABSTRACT The IME2 gene is one of the key regulators of the initiation of meiosis in budding yeast. This gene is repressed during mitosis through the repressive chromatin structure at the promoter, which is maintained by the Rpd3-Sin3 histone deacetylase (HDAC) complex. IME2 expression in meiosis requires Gcn5/histone acetyltransferase, the transcriptional activator Ime1, and the chromatin remodeler RSC; however, the molecular basis of IME2 activation had not been previously defined. We found that, during mitotic growth, a nucleosome masked the TATA element of IME2, and this positioning depended on HDAC. This chromatin structure was remodeled at meiosis by RSC that was recruited to TATA by Ime1. Stable tethering of Ime1 to the promoter required the presence of Gcn5. Interestingly, Ime1 binding to the promoter was kept at low levels during the very early stages in meiosis, even when the levels of Ime1 and histone H3 acetylation at the promoter were at their highest, making a 4- to 6-h delay of the IME2 expression from that of IME1. HDAC was continuously present at the promoter regardless of the transcriptional condition of IME2, and deletion of RPD3 allowed the IME2 expression shortly after the expression of IME1, suggesting that HDAC plays a role in regulating the timing of IME2 expression.

Histone acetyltransferase-1 regulates integrity of cytosolic histone H3–H4 containing complex

2008 ◽  
Vol 373 (4) ◽  
pp. 624-630 ◽  
Author(s):  
Hirak Kumar Barman ◽  
Yasunari Takami ◽  
Hitoshi Nishijima ◽  
Kei-ichi Shibahara ◽  
Fumiyuki Sanematsu ◽  
...  
Keyword(s):  
Histone Acetyltransferase ◽  
Histone H3

scholarly journals The Carboxyl Terminus of Rtt109 Functions in Chaperone Control of Histone Acetylation

2013 ◽  
Vol 12 (5) ◽  
pp. 654-664 ◽  
Author(s):  
Ernest Radovani ◽  
Matthew Cadorin ◽  
Tahireh Shams ◽  
Suzan El-Rass ◽  
Abdel R. Karsou ◽  
...  
Keyword(s):  
Histone Acetyltransferase ◽  
Histone H3 ◽  
Chromatin Assembly ◽  
Carboxyl Terminus ◽  
Histone Chaperones ◽  
Content Type ◽  
Histone H3 Acetylation ◽  
H3 Acetylation

ABSTRACT Rtt109 is a fungal histone acetyltransferase (HAT) that catalyzes histone H3 acetylation functionally associated with chromatin assembly. Rtt109-mediated H3 acetylation involves two histone chaperones, Asf1 and Vps75. In vivo , Rtt109 requires both chaperones for histone H3 lysine 9 acetylation (H3K9ac) but only Asf1 for full H3K56ac. In vitro , Rtt109-Vps75 catalyzes both H3K9ac and H3K56ac, whereas Rtt109-Asf1 catalyzes only H3K56ac. In this study, we extend the in vitro chaperone-associated substrate specificity of Rtt109 by showing that it acetylates vertebrate linker histone in the presence of Vps75 but not Asf1. In addition, we demonstrate that in Saccharomyces cerevisiae a short basic sequence at the carboxyl terminus of Rtt109 (Rtt109C) is required for H3K9ac in vivo . Furthermore, through in vitro and in vivo studies, we demonstrate that Rtt109C is required for optimal H3K56ac by the HAT in the presence of full-length Asf1. When Rtt109C is absent, Vps75 becomes important for H3K56ac by Rtt109 in vivo . In addition, we show that lysine 290 (K290) in Rtt109 is required in vivo for Vps75 to enhance the activity of the HAT. This is the first in vivo evidence for a role for Vps75 in H3K56ac. Taken together, our results contribute to a better understanding of chaperone control of Rtt109-mediated H3 acetylation.

scholarly journals Nucleosomal Asymmetry Shapes Histone Mark Binding and Promotes Poising at Bivalent Domains

2021 ◽  
Author(s):  
Elana Bryan ◽  
Marie Warburton ◽  
Kimberly M. Webb ◽  
Katy A. McLaughlin ◽  
Christos Spanos ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Neuronal Differentiation ◽  
Histone Acetyltransferase ◽  
Histone H3 ◽  
Embryonic Stem ◽  
Histone Mark ◽  
Developmental Genes ◽  
Chromatin Proteins ◽  
And Function

SummaryPromoters of developmental genes in embryonic stem cells (ESCs) are marked by histone H3 lysine 4 trimethylation (H3K4me3) and H3K27me3 in an asymmetric nucleosomal conformation, with each sister histone H3 carrying only one mark. These bivalent domains are thought to poise genes for timely activation upon differentiation. Here we show that asymmetric bivalent nucleosomes recruit repressive H3K27me3 binders but fail to enrich activating H3K4me3 binders, despite presence of H3K4me3, thereby promoting a poised state. Strikingly, the bivalent mark combination further attracts chromatin proteins that are not recruited by each mark individually, including the histone acetyltransferase complex KAT6B (MORF). Knockout of KAT6B blocks neuronal differentiation, demonstrating that bivalency-specific readers are critical for proper ESC differentiation. These findings reveal how histone mark bivalency directly promotes establishment of a poised state at developmental genes, while highlighting how nucleosomal asymmetry is critical for histone mark readout and function.

scholarly journals Recruitment of SWI/SNF by Gcn4p Does Not Require Snf2p or Gcn5p but Depends Strongly on SWI/SNF Integrity, SRB Mediator, and SAGA

2003 ◽  
Vol 23 (23) ◽  
pp. 8829-8845 ◽  
Author(s):  
Sungpil Yoon ◽  
Hongfang Qiu ◽  
Mark J. Swanson ◽  
Alan G. Hinnebusch
Keyword(s):  
Target Genes ◽  
Histone Acetyltransferase ◽  
Histone H3 ◽  
Nucleosome Remodeling ◽  
Cooperative Interactions ◽  
Multiple Contacts ◽  
H3 Acetylation ◽  
Distinct Subunit

ABSTRACT The nucleosome remodeling complex SWI/SNF is a coactivator for yeast transcriptional activator Gcn4p. We provide strong evidence that Gcn4p recruits the entire SWI/SNF complex to its target genes ARG1 and SNZ1 but that SWI/SNF is dispensable for Gcn4p binding to these promoters. It was shown previously that Snf2p/Swi2p, Snf5p, and Swi1p interact directly with Gcn4p in vitro. However, we found that Snf2p is not required for recruitment of SWI/SNF by Gcn4p nor can Snf2p be recruited independently of other SWI/SNF subunits in vivo. Snf5p was not recruited as an isolated subunit but was required with Snf6p and Swi3p for optimal recruitment of other SWI/SNF subunits. The results suggest that Snf2p, Snf5p, and Swi1p are recruited only as subunits of intact SWI/SNF, a model consistent with the idea that Gcn4p makes multiple contacts with SWI/SNF in vivo. Interestingly, Swp73p is necessary for efficient SWI/SNF recruitment at SNZ1 but not at ARG1, indicating distinct subunit requirements for SWI/SNF recruitment at different genes. Optimal recruitment of SWI/SNF by Gcn4p also requires specific subunits of SRB mediator (Gal11p, Med2p, and Rox3p) and SAGA (Ada1p and Ada5p) but is independent of the histone acetyltransferase in SAGA, Gcn5p. We suggest that SWI/SNF recruitment is enhanced by cooperative interactions with subunits of SRB mediator and SAGA recruited by Gcn4p to the same promoter but is insensitive to histone H3 acetylation by Gcn5p.

scholarly journals Histone H3 lysine 56 acetylation by Rtt109 is crucial for chromosome positioning

2008 ◽  
Vol 183 (4) ◽  
pp. 641-651 ◽  
Author(s):  
Shin-ichiro Hiraga ◽  
Sotirios Botsios ◽  
Anne D. Donaldson
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Dna Replication ◽  
Histone Acetyltransferase ◽  
Nuclear Periphery ◽  
Histone H3 ◽  
Epigenetic Inheritance ◽  
S Phase ◽  
Chromosome Localization ◽  
Chromosome Domains ◽  
H3k56 Acetylation

Correct intranuclear organization of chromosomes is crucial for many genome functions, but the mechanisms that position chromatin are not well understood. We used a layered screen to identify Saccharomyces cerevisiae mutants defective in telomere localization to the nuclear periphery. We find that events in S phase are crucial for correct telomere localization. In particular, the histone chaperone Asf1 functions in telomere peripheral positioning. Asf1 stimulates acetylation of histone H3 lysine 56 (H3K56) by the histone acetyltransferase Rtt109. Analysis of rtt109Δ and H3K56 mutants suggests that the acetylation/deacetylation cycle of the H3K56 residue is required for proper telomere localization. The function of H3K56 acetylation in localizing chromosome domains is not confined to telomeres because deletion of RTT109 also prevents the correct peripheral localization of a newly identified S. cerevisiae “chromosome-organizing clamp” locus. Because chromosome positioning is subject to epigenetic inheritance, H3K56 acetylation may mediate correct chromosome localization by facilitating accurate transmission of chromatin status during DNA replication.

scholarly journals ORC, MCM, and Histone Hyperacetylation at the Kaposi's Sarcoma-Associated Herpesvirus Latent Replication Origin

2004 ◽  
Vol 78 (22) ◽  
pp. 12566-12575 ◽  
Author(s):  
William Stedman ◽  
Zhong Deng ◽  
Fang Lu ◽  
Paul M. Lieberman
Keyword(s):  
Dna Replication ◽  
Replication Origin ◽  
Kaposi's Sarcoma ◽  
Histone Acetyltransferase ◽  
Histone H3 ◽  
Kaposi’S Sarcoma ◽  
Latently Infected ◽  
Infected Cells ◽  
Kaposi's Sarcoma Associated Herpesvirus ◽  
Kaposi’S Sarcoma Associated Herpesvirus

ABSTRACT The viral genome of Kaposi's sarcoma-associated herpesvirus (KSHV) persists as an extrachromosomal plasmid in latently infected cells. The KSHV latency-associated nuclear antigen (LANA) stimulates plasmid maintenance and DNA replication by binding to an ∼150-bp region within the viral terminal repeats (TR). We have used chromatin immunoprecipitation assays to demonstrate that LANA binds specifically to the replication origin sequence within the KSHV TR in latently infected cells. The latent replication origin within the TR was also bound by LANA-associated proteins CBP, double-bromodomain-containing protein 2 (BRD2), and the origin recognition complex 2 protein (ORC2) and was enriched in hyperacetylated histones H3 and H4 relative to other regions of the latent genome. Cell cycle analysis indicated that the minichromosome maintenance complex protein, MCM3, bound TR in late-G1/S-arrested cells, which coincided with the loss of histone H3 K4 methylation. Micrococcal nuclease studies revealed that TRs are embedded in a highly ordered nucleosome array that becomes disorganized in late G1/S phase. ORC binding to TR was LANA dependent when reconstituted in transfected plasmids. DNA affinity purification confirmed that LANA, CBP, BRD2, and ORC2 bound TR specifically and identified the histone acetyltransferase HBO1 (histone acetyltransferase binding to ORC1) as a potential TR binding protein. Disruption of ORC2, MCM5, and HBO1 expression by small interfering RNA reduced LANA-dependent DNA replication of TR-containing plasmids. These findings are the first demonstration that cellular replication and origin licensing factors are required for KSHV latent cycle replication. These results also suggest that the KSHV latent origin of replication is a unique chromatin environment containing histone H3 hyperacetylation within heterochromatic tandem repeats.

scholarly journals Chaperone Control of the Activity and Specificity of the Histone H3 Acetyltransferase Rtt109

2008 ◽  
Vol 28 (13) ◽  
pp. 4342-4353 ◽  
Author(s):  
Jeffrey Fillingham ◽  
Judith Recht ◽  
Andrea C. Silva ◽  
Bernhard Suter ◽  
Andrew Emili ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Histone Acetyltransferase ◽  
Histone H3 ◽  
Histone Chaperone ◽  
Genetic Interactions ◽  
Whole Genome ◽  
Genome Screen ◽  
Associated Lesions

ABSTRACT Acetylation of Saccharomyces cerevisiae histone H3 on K56 by the histone acetyltransferase (HAT) Rtt109 is important for repairing replication-associated lesions. Rtt109 purifies from yeast in complex with the histone chaperone Vps75, which stabilizes the HAT in vivo. A whole-genome screen to identify genes whose deletions have synthetic genetic interactions with rtt109Δ suggests Rtt109 has functions in addition to DNA repair. We show that in addition to its known H3-K56 acetylation activity, Rtt109 is also an H3-K9 HAT, and we show that Rtt109 and Gcn5 are the only H3-K9 HATs in vivo. Rtt109's H3-K9 acetylation activity in vitro is enhanced strongly by Vps75. Another histone chaperone, Asf1, and Vps75 are both required for acetylation of lysine 9 on H3 (H3-K9ac) in vivo by Rtt109, whereas H3-K56ac in vivo requires only Asf1. Asf1 also physically interacts with the nuclear Hat1/Hat2/Hif1 complex that acetylates H4-K5 and H4-K12. We suggest Asf1 is capable of assembling into chromatin H3-H4 dimers diacetylated on both H4-K5/12 and H3-K9/56.

scholarly journals Epigenetic Control of the Immune Escape Mechanisms in Malignant Carcinomas

2007 ◽  
Vol 27 (22) ◽  
pp. 7886-7894 ◽  
Author(s):  
A. Francesca Setiadi ◽  
Muriel D. David ◽  
Robyn P. Seipp ◽  
Jennifer A. Hartikainen ◽  
Rayshad Gopaul ◽  
...  
Keyword(s):  
Rna Polymerase Ii ◽  
Antigen Processing ◽  
Molecular Mechanisms ◽  
Histone Acetyltransferase ◽  
Immune Escape ◽  
Histone H3 ◽  
Histone H3 Acetylation ◽  
Low Levels ◽  
Immune Escape Mechanisms ◽  
H3 Acetylation

ABSTRACT Downregulation of the transporter associated with antigen processing 1 (TAP-1) has been observed in many tumors and is closely associated with tumor immunoevasion mechanisms, growth, and metastatic ability. The molecular mechanisms underlying the relatively low level of transcription of the tap-1 gene in cancer cells are largely unexplained. In this study, we tested the hypothesis that epigenetic regulation plays a fundamental role in controlling tumor antigen processing and immune escape mechanisms. We found that the lack of TAP-1 transcription in TAP-deficient cells correlated with low levels of recruitment of the histone acetyltransferase, CBP, to the TAP-1 promoter. This results in lower levels of histone H3 acetylation at the TAP-1 promoter, leading to a decrease in accessibility of the RNA polymerase II complex to the TAP-1 promoter. These observations suggest that CBP-mediated histone H3 acetylation normally relaxes the chromatin structure around the TAP-1 promoter region, allowing transcription. In addition, we found a hitherto-unknown mechanism wherein interferon gamma up-regulates TAP-1 expression by increasing histone H3 acetylation at the TAP-1 promoter locus. These findings lie at the heart of understanding immune escape mechanisms in tumors and suggest that the reversal of epigenetic codes may provide novel immunotherapeutic paradigms for intervention in cancer.

Sign in / Sign up

Export Citation Format

Share Document