HomeLarge Type Edition
HOME ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Services
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
PubMed
Right arrow PubMed Citation
The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 57:B93-B98 (2002)
© 2002 The Gerontological Society of America

Histone Acetyltransferase Activities of cAMP-Regulated Enhancer-Binding Protein and p300 in Tissues of Fetal, Young, and Old Mice

Qiang Lia, Hengyi Xiaoa and Ken-ichi Isobea

a Department of Basic Gerontology, National Institute for Longevity Sciences, Aichi, Japan

Ken-ichi Isobe, Department of Basic Gerontology, National Institute for Longevity Sciences, 36-3, Gengo, Morioka-cho, Obu, Aichi, 474-8522, Japan E-mail: kenisobe{at}nils.go.jp.

Decision Editor: John A. Faulkner, PhD


   Abstract
Top
 Abstract
Methods
 Results
 Discussion
 References
 
CBP, a protein that binds to cyclic adenosine monophosphate-regulated enhancer-binding protein, and homologue protein, p300, have histone acetyltransferase (HAT) activity and are important in gene transcription, although their physiological functions in vivo remain to be further elucidated. By using immunoprecipitation and HAT activity assay we have found that p300 and CBP have similar tissue patterns of HAT activities, with the highest level in the brain, a relatively high level in the lung, spleen, and heart, an intermediate level in testes and muscle, and a lower level in liver and kidney; that HAT activities of p300 and CBP are relatively stable with advancing age in most examined tissues, but in liver, muscle, and testes, the activities are attenuated with aging; and that HAT activities of p300 and CBP are high in the brain and liver of E14 fetal and newborn mice. These data suggest that the HAT activities of p300 and CBP are important for gene transcription involved in tissue-specific expression, aging, and developing processes.

CYCLIC adenosine monophosphate (cAMP)-regulated gene expression frequently involves a DNA element known as the cAMP-regulated enhancer, or CRE (1)(2). Many transcription factors bind to this element, including a specific CRE-binding protein (CREB), which is activated as a result of phosphorylation by protein kinase A (1)(2). Phosphorylated CREB interacts with a 265-Kda nuclear protein termed CBP (for CREB-binding protein), which bridges the CRE/CREB complex to components of the basal transcriptional apparatus (1)(2). Recently it has been shown that CBP belongs to a new family of coactivators/regulators of transcription that also includes p300, an adenovirus E1A targeted nuclear protein (3)(4)(5)(6)(7)(8). p300–CBP can interact with a variety of cellular and virus proteins, as well as with transcription machinery (9)(10). Most proteins that bind to p300–CBP are transcription factors. In addition, p300–CBP has intrinsic histone acetyltranferase (HAT) activity that has been proved to be critical for a large number of regulated DNA-binding transcriptions (11)(12)(13). The acetylation of histones is thought to be involved in the destabilization and restructuring of nucleosomes, which is probably a crucial event in the control of the accessibility of DNA templates to transcriptional factors (14)(15)(16)(17). A current working hypothesis is that the recruitment of coactivators with HAT activity by promoter-bound transcription factors results in the acetylation of histone residues of nearby nucleosomes, which increases the accessibility of the DNA to the transcription machinery (17)(18)(19). Furthermore, recent studies have also shown that histones are not the only substrates of p300–CBP; p53 and some basal transcription factors (TF), such as TFIIE, TFIIF, erythroid Kruppel-like factor (EKLF), and GATA-1, are also acetylated by p300–CBP (20)(21)(22)(23). Thus it appears that p300–CBP participates in transcription by forming the scaffold that allows various classes of transcriptional regulators to interact with specific domains within the chromatin (23). The interaction of p300–CBP with numerous DNA-binding regulatory proteins integrates and transduces signals for control of the cell cycle, differentiation, DNA repair, and apoptosis (17). Hence, the regulation of p300–CBP acetyltransferase activity may represent a mechanism for the integration of diverse signaling pathways (24).

Structure and functions of p300 and CBP have been extensively studied in in vitro systems. Although p300 and CBP are greatly important in gene expression, the HAT activities of these proteins in normal tissues have never been examined. Here, we present the data of p300 and CBP HAT activities in normal tissues of young and old mice.


   Methods
Top
 Abstract
 Methods
Results
 Discussion
 References
 
Animals
Male C57/BL6J mice that were either 3 or 24 months of age were obtained from the animal center of the National Institute for Longevity Science (NILS) and sacrificed by ether and bleeding. All the mice used were bred in NILS's animal center in a strictly pathogen-free environment. Several viruses were periodically checked. The tissues of kidney, heart, liver, brain, muscle (quadriceps femurs), lung, spleen, and testes were removed, excised, and immediately put into a Lysis buffer and homogenized with an electric homogenizer. The liver and the brain of C57/BL6J murine fetus (gestation 14 days), newborn (1 day), and 1-month-old mice were also obtained and were treated as described above.

Immunoprecipitation
The freshly isolated tissues were immediately homogenized by using a Lysis buffer containing 1% Nonidet P-40, 0.5% sodium deoxycholate, 0.1% sodium dodecyl sulfate (SDS), 150 mM sodium chloride, 50 mM Tris (pH 7.4), and 20 mM phosphate buffer (pH 7.4) supplemented with 5 mM dithiothreitol, 1 mM ethylenediamine tetra-acetic acid (EDTA), and freshly prepared protease and phosphatase inhibitors—10 mM sodium fluoride, 1 mM sodium vanadate, 1 mM phenylmethylsulfonyl fluoride (PMSF) and aprotinin, leupeptin, and pepstatin at 10 µg/ml each. The tissues were kept on ice for 30 minutes and then centrifuged at 15,000 rpm by a tabletop centrifuge for 30 minutes at 4°C. The supernatants were carefully isolated and the protein concentrations were determined by the method of Bradford assay with the Bio-Rad protein assay dye reagent (Bio-Rad, Tokyo, Japan). One milligram of protein was diluted in 1 ml of RIPA buffer and precleared by using rabbit preimmune serum (Santa Cruz Biotechnology, Santa Cruz, CA) and protein-G/sepharose beads (Amersham Pharmacia Biotech, Buckinghamshire, UK) for 2 hours at 4°C. The supernatants were incubated with the specific rabbit polyclonal antibodies for CBP (Santa Cruz, A22), p300 (Santa Cruz, N-15), or a normal rabbit IgG (Santa Cruz), in the presence of protein-G/sepharose beads at 4°C overnight. The Sepharose beads were then washed five times with RIPA buffer and used for the HAT assay.

HAT Assay
For the HAT activities of p300 and CBP to be measured, immunoprecipitation from different tissues was first performed as described above; then filter binding assays were done as Ogryzko and colleagues described (11) with minor modifications. After immunoprecipitation and being washed with RIPA buffer, samples were washed twice further with HAT assay buffer containing 50 mM Tris-HCl (pH 8.0), 10% glycerol, 1 mM PMSF, 1 mM dithiothylitol, and 10 mM sodium butyrate. They were incubated at 30°C for 60 minutes in 30 µl of HAT assay buffer containing 0.25 µCi of [3H] acetyl coA (2–10 Ci/mmol, 250 µCi/ml, mCi/mmol, Amersham Pharmacia Biotech, Buckinghamshire, UK) and 50 µg/ml calf thymus histone (Sigma Chemical, St. Louis, MO). After incubation, the reaction mixture was spotted onto Whatman P-81 phosphocellulose filter paper and washed four times with 0.2 M sodium carbonate buffer (pH 9.2) at room temperature. The dried filters were counted in a liquid scintillation counter. For each specific HAT activity, the data were subtracted from normal rabbit IgG. For detecting the total cellular HAT activity, the homogenate cell lysates containing 15 µg of protein were diluted with HAT assay buffer to a final volume of 30 µl. After 0.25 µCi of [3H] acetyl coA and 15 µg/ml of calf thymus histone were added, the assay process was in accordance with the method stated above.

Statistical Analysis
Data are expressed as mean ± standard error of the mean. A one-way analysis of variance (ANOVA) was used to evaluate differences among age groups.

RNA Isolation and Northern Blot Analysis
Total RNA was extracted with Trizol (Invitrogen, Carlsbad, CA) from mouse tissues. Samples of 20 µg of total RNA were denatured, separated by electrophoresis in a 1% agarose gel containing formaldehyde, and transferred to GeneScreen membranes (NEN, DuPont, MA). The membranes were prehybridized and then hybridized with p300 cDNA probes donated by Antonio Giordano labeled with [{alpha}-32P] deoxy cytidine triphosphate using a random primer labeling system (Amersham Pharmacia Biotech, Buckinghamshire, UK). After hybridization, the membranes were washed and exposed to x-ray film. All blots were rehybridized with a glyceraldehyde-3-phosphate dehydrogenase (GAPDH) cDNA probe to normalize for mRNA loading differences. For the contents of mRNA to be quantified in the cells, the membranes were exposed to imaging plates, and radioactivities were measured with a bioimage analyzer (Fijix BAS 1500, Fuji Film, Tokyo).


   Results
Top
 Abstract
 Methods
 Results
Discussion
 References
 
Tissue Patterns of p300 and CBP HAT Activities
Table 1 shows the HAT activity patterns of p300 and CBP in different tissues of normal young and old mice, respectively. Although the HAT activities of CBP were slightly higher than that of p300, the tissue patterns of HAT activities of CBP and p300 were quite similar. The highest HAT activities were observed in the brain in both young and old mice. The lung, spleen, and heart had relatively high HAT activities. The testes and the muscle had intermediate HAT activities and the liver had low HAT activities. Among the tissues examined, the kidney showed the lowest HAT activities of p300 and CBP. These results revealed the tissue-specific patterns of the HAT activities of p300 and CBP in normal murine tissues and the similar enzymatic distribution of p300 and CBP in murine tissues.


View this table:
[in this window]
[in a new window]
  		Table 1. HAT Activity Assay of p300 and CBP in Different Tissues of Young and Old Mice

 
To ensure the specificity of p300 and CBP in our HAT assay, we designed our experimental protocols especially at three points. First, we used a highly stringent Lysis buffer for cell lyzing and immunoprecipitation, because the deoxycholate and SDS contained in this buffer will diminish most, if not all, of the nonspecific protein interaction. Second, the data were subtracted from nonspecific IgG controls for every sample. The measuring values of specific HAT activity were always higher than 1000-fold of normal IgG controls. The data shown in Table 1 were the specific values subtracted from the control value. Third, we selectively used the antibodies without cross-reaction between p300 and CBP for immunoprecipitation, according to the information of the manufacturers (Santa Cruz). In fact, we confirmed the specificities of both the anti-p300 antibody and anti-CBP antibody we used for immunoprecipitation by Western blotting (data not shown).

Tissue Patterns of Total Cellular HAT Activities
To further understand the contribution of p300–CBP HAT activities in different tissues, we assayed the total cellular HAT activity by using total cell lysate. The results are shown in Table 2 . When comparing Table 1 with Table 2 , we found that the total cellular HAT activities not only had their own tissue patterns, which were significantly distinct from the tissue paterns of CBP and p300 HAT activities, but also showed even greater tissue diversity. The spleen and lung had the highest total cellular HAT activities; the heart, brain, muscle, and liver showed modest total cellular HAT activities; the kidney had very low total mixed HAT activities; and the total cellular HAT activities of the testes were undetectable. Taken together, these results suggested that, as did p300–CBP HAT activities, the total cellular HAT activities had their own distinct tissue patterns also.


View this table:
[in this window]
[in a new window]
  		Table 2. Total HAT Activity Assay in Different Tissues of Young and Old Mice

 
Effect of Aging on HAT Activity of p300 and CBP
Table 1 also shows that there were no significant changes of p300 and CBP HAT activities with advancing age in most tissues examined, such as kidney, heart, brain, lung, and spleen. However, the HAT activities of both CBP and p300 in liver, muscle, and testes were significantly decreased with advancing age. Aging also had an effect on total cellular HAT activities. Table 2 shows that the total HAT activity of the spleen was significantly elevated in the 24-month-old group, whereas in other tissues no age-related changes of the total HAT activities were observed. These results indicated that there were age-related changes of p300–CBP HAT activities in liver, muscle, and testes, and there were changes of total cellular HAT activities in the spleen. However, in other tissues examined, the HAT activities of p300 and CBP and the total HAT activities were kept relatively stable in advancing age.

Effect of Development on HAT Activities of CBP and p300 in Brain and Liver
To understand if CBP and p300 HAT activities are associated with development, we further examined p300 and CBP HAT activities of liver and brain in fetal (E14), newborn (1 day) and 1-month-old mice. The results are shown in Table 3 . The p300 and CBP HAT activities of liver and brain in fetal and newborn mice were much higher than those of other age groups, and those were downregulated with development. The most significant changes of HAT activities in the brain were observed between newborn and 1-month-old mice, whereas in liver, the decrease of HAT activities was more obvious between fetal and newborn mice than between newborn and 1-month-old mice. These results suggest that the HAT activities of p300 and CBP may play an important role in the development of brain and liver.


View this table:
[in this window]
[in a new window]
  		Table 3. Changes of p300 and CBP Activities in Liver and Brain With Development

 
The mRNA Expression of p300 in Liver at Different Ages
In order to further clarify the great changes of p300 (CBP) HAT activities in liver, we examined the p300 mRNA expression of liver tissues from fetal (E14) to aged (24-month-old) mice. The p300 mRNA of E14 fetal mice was much higher than that of 1-month-old mice. The level of p300 mRNA gradually decreased with advancing age (Fig. 1), although the levels of p300 mRNA of other tissues were relatively stable in advancing age (data not shown).



View larger version (63K):
[in this window]
[in a new window]
  		Figure 1. The expression of p300 mRNA in murine liver: 20 µg of total RNA was subjected to Northern blot analysis probed with segment of p300 cDNA, which was followed by a glyceraldehyde-3-phosphate dehydrogenase (GAPDH) probe to normalize for loading differences. F = 14-day-old murine fetus; M = month.

 

   Discussion
Top
 Abstract
 Methods
 Results
 Discussion
References
 
Tissue Patterns of p300 and CBP HAT Activities
Although p300 and CBP have been reported to be ubiquitously expressed in cell lines derived from different tissues, we presented here that HAT activities of both p300 and CBP have distinct tissue patterns (Table 1 and Table 2 ). This distinct tissue pattern of HAT activities suggests that, before functioning as the important coactivators of gene transcription, p300 and CBP are regulated by the still unknown mechanism(s) for their own HAT activities. We found significant differences in tissue patterns between p300 and CBP HAT activities and total cellular HAT activities. The highest HAT activity of p300 and CBP versus relatively low total cellular HAT activities in the brain indicated that p300 and CBP might play important roles for gene transcription in the brain. In contrast, the very high total cellular HAT activities over the HAT activities of p300 and CBP in the spleen and lung might mean that the HAT other than p300–CBP activities were also important in transcriptional regulation. One extreme example we found was in the testes. Testes showed high HAT activities of p300 and CBP, but the total cellular HAT activities were undetectable. Given that we used more than 60-fold of cell lysates (1 mg) for p300–CBP immunoprecipitation and their specific HAT assay than those (15 µg) for total cellular HAT assay, the higher HAT activities of p300–CBP than total cellular HAT activities is not unreasonable. However, in comparison with other tissues with similar p300–CBP HAT activities, such as the heart, the total cellular HAT activities in testes were really very weak. Therefore, we hypothesize here that the p300 and CBP might be the main HAT in testes, and their activities might be essential in testis development and spermatogenesis. Further studies should be carried out to investigate the tissue patterns of other HATs, such as p300/cyclic AMP responsible element binding protein-associated factor (25), general control nonrepressed 5, and so on.

Effect of Aging on HAT Activity of p300 and CBP
There have been no reports about the effect of aging on HAT activities of CBP and p300. The data presented herein showed that in most examined tissues, such as the kidney, brain, heart, lung, and spleen, HAT activities of p300 and CBP are considerably stable with advancing age, indicating that HAT activities of p300 and CBP are associated with the transcription activation–regulation of genes responsible for the physiological changes of aging. However, in liver, muscle and testes, HAT activities of p300 and CBP were attenuated with aging, although the underlying mechanisms are unclear. It is interesting to find that the total cellular HAT activity in spleen of 24-month-old mice is obviously elevated whereas the HAT activities of p300 and CBP are kept unchanged with advancing age. The spleen is an immune organ and there are reports that demonstrate the changes of T-cell subpopulations and related cytokine production of the spleen with aging (26)(27). We suppose, therefore, that the increased total cellular HAT activities in spleen of old mice are concerned with these changes and HATs other than p300 and CBP may be involved. The changes of HAT activities in the spleen of old mice might be due to an increased sensitivity of the old mice to infection. However, this possibility is negligible, because our animal center is a strictly pathogen-free environment. In brief, our results support that HAT activities of p300 and CBP are differently changed in normal murine tissues with advancing age, and further studies are needed for elucidating the mechanism for regulation of p300 and CBP HAT activity in liver, muscle, and testes.

The Changes of p300 and CBP HAT Activities With Development
The important functions of p300 and CBP in development have been proved by gene targeting. The homozygous CBP-deficient mice died around E10.5–E12.5, apparently as a result of massive hemorrhage caused by defective blood vessel formation in the central nervous system, and they exhibited apparent development retardation as well as delays in both primitive and definitive hematopoiesis (28). CBP-deficient murine embryos also exhibited defective neural tube closure (28). Similar to the exhibitions of the CBP-deficient mice, the mice lacking a functional p300 gene died between days 9 and 11.5 of gestation, exhibiting defects in neurulation, cell proliferation, and heart development (29). Cells derived from p300-deficient embryos also displayed specific transcriptional defects and poor proliferation (29). Our data showing much higher HAT activities of p300 and CBP in brains of the E14 fetus and newborns than in those of other age groups, and the markedly downregulated HAT activities of p300 and CBP with the development of the brain (Table 3 ) were consistent with the reports stated above. Our results indicate that HAT activities of p300 and CBP play an important role in the development of brain. Furthermore, our findings that very high HAT activities of p300 and CBP were observed in liver of 14-day gestational fetuses and that they subsequently sharply declined with liver development appears to support the notion that HAT activities of p300 and CBP are associated with the hematopoiesis of fetal liver. Liver is one of the main hematopoietic tissues of the fetus during gestation. Murine hepatic hematopoiesis started at 11 days gestation (30), and different types of Spleen-colony-forming units attained peaks at 13–14 days gestation (31); after that, the hepatic hematopoiesis quickly decreased with development. The changes of p300 and CBP HAT activities in liver were in accordance with reports that CBP-deficient mice exhibited delays in both primitive and definitive hematopoiesis and appear to suggest that HAT activities of p300 and CBP are responsible for fetal liver hematopoiesis.

Taken together, HAT activities of p300 and CBP have distinct tissue patterns and maintain considerable stability with advancing age in most murine tissues except liver, muscle, and testes. The alteration of p300–CBP activation might be associated with the development of brain and fetal hepatic hematopoiesis.

Histone Acetylation in Aging
Ogryzko and colleagues (32) showed that two histone deacetylase inhibitors, sodium butyrate and trichostatin A, dramatically reduced the human diploid fibroblast proliferative life span. We have shown that histone deacetylase inhibitor (sodium butyrate or trichostatin A) induces a cellular senescence-like phenotype in NIH3T3 cells and enhances p21 promoter activity in this cell line (33). We also found that p300 works as a coactivator of trichostatin A-induced p21 promoter activity (34). Meanwhile, Wagner and colleagues (35) found a significant decrease in the abundance of histone deacetylase-1 in senescent cells by Northern blot and Western blot analyses. These results strongly suggest that, on one hand, histone acetylation may play some role in cellular senescence. On the other hand, to our knowledge there have been no reports that have proven the role of histone acetylation in the in vivo aging of mammals. To our knowledge, the data presented here are the first report concerned with this issue. We think they will be useful in the development of our understanding of the role of histone acetylation in the in vivo aging process from the view of gene transcription.


   Acknowledgments
 
This work was supported by the Fund for Comprehensive Research on Aging and Health.

Received May 22, 2001

Accepted October 25, 2001


   References
Top
 Abstract
 Methods
 Results
 Discussion
 References
 

  1. Chriviaq JC, Kwok RP, Lamb N, Hagiwara M, Montminy MR, Goodman R, 1993. Phosphorylated CREB binds specifically to the nuclear protein CBP. Nature. 365: (6449) 855-859. [Medline]
  2. Andrisani OM, 1999. CREB-mediated transcription control. Crit Rev Eukaryot Gene Expr. 9: (1) 19-32. [Medline]
  3. Eckner R, Ewen ME, Newsome D, et al. 1994. Molecular cloning and functional analysis of the adenovirus E1A-associated 300-kDa protein (p300) reveals a protein with properties of a transcriptional adapter. Genes Dev. 8:869-884. [Abstract/Free Full Text]
  4. Arany Z, Newsome D, Oldread E, Livingston DM, Eckner R, 1995. A family of transcriptional adaptor proteins targeted by the E1A oncoprotein. Nature. 374:81-84. [Medline]
  5. Lundblad JR, Kwok RPS, Laurance ME, Harter ML, Goodman RH, 1995. Adenoviral E1A-associated protein p300 as a functional homologue of the transcriptional co-activator CBP. Nature. 374:85-88. [Medline]
  6. Egan C, Jelsma TN, Howe JA, Bayley ST, Ferguson B, Branton PE, 1988. Mapping of cellular protein-binding sites on the products of early-region 1A of human adenovirus type 5. Mol Cell Biol. 8:3955-3959. [Abstract/Free Full Text]
  7. Whyte P, Williamson NM, Harlow E, 1989. Cellular targets for transformation by the adenovirus E1A proteins. Cell. 56:67-75. [Medline]
  8. Yaciuk P, Moran E, 1991. Analysis with specific polyclonal antiserum indicates that the E1A-associated 300 kDa product is a stable nuclear phosphoprotein that undergoes cell cycle phase-specific modification. Mol Cell Biol. 11: (11) 5389-5397. [Abstract/Free Full Text]
  9. Giles RH, Peters DJM, Breuning MH, 1998. Conjunction dysfunction: CBP/p300 in human disease. Trends Genet. 14:178-183. [Medline]
  10. Janknecht R, Hunter TA, 1996. A growing coactivator network. Nature. 383:22-23. [Medline]
  11. Ogryzko VV, Schiltz RL, Russanova V, Howard BH, Nakatani Y, 1996. The transcriptional coactivators p300 and CBP are histone acetyltransferases. Cell. 87:953-959. [Medline]
  12. Andrew J, Kouzarides T, 1996. The CBP co-activator is a histone acetyltransferase. Nature. 384:631-643.
  13. Ait-Si-Ali S, Ramirez S, Barre F-X, et al. 1998. Histone acetyltransferase activity of CBP is controlled by cycle-dependent kinases and oncoprotein E1A. Nature. 396:184-186. [Medline]
  14. Grunstein M, 1997. Histone acetylation in chromatin structure and transcription. Nature. 389:349-352. [Medline]
  15. Mizzen CA, Allis CD, 1998. Linking histone acetylation to transcription regulation. Cell Mol Life Sci. 54:6-20. [Medline]
  16. Struhl K, 1998. Histone acetylation and transcriptional regulatory mechanism. Genes Dev. 12:599-606. [Free Full Text]
  17. Kornberg RD, Lorch Y, 1999. Twenty-five years of the nucleosome, fundamental particle of the eukaryote chromosome. Cell. 98:285-294. [Medline]
  18. Imhof A, Yang XJ, Ogryzko VV, Nakatani Y, Wolff AP, Ge H, 1997. Acetylation of general transcription factors by histone acetyltransferase. Curr Biol. 7:689-692. [Medline]
  19. Ugai H, Uchida K, Kawasaki H, Yokoyama KK, 1999. The coactivator p300 and CBP have different functions during the differentiation of F9 cells. J Mol Med. 77;481–494:
  20. Gu W, Shi X, Roeder RG, 1997. Synergistic activation of transcription by CBP and p53. Nature. 387:819-823. [Medline]
  21. Zhang W, Bieker JJ, 1998. Acetylation and modulation of erythroid Kruppel-like factor (EKLF) activity by interaction with histone acetyltransferases. Proc Natl Acad Sci USA. 95:9855-9860. [Abstract/Free Full Text]
  22. Boyes J, Byfield P, Nakatani Y, Ogryzko V, 1998. Regulation of activity of the transcription factor GATA-1 by acetylation. Nature. 396:594-598. [Medline]
  23. Perissi V, Dasen JS, Kurokawa R, et al. 1999. Factor-specific modulation of CREB-binding protein acetyltransferase activity. Proc Natl Acad Sci USA. 96:3652-3657. [Abstract/Free Full Text]
  24. Yang XJ, Ogryzko VV, Nishikawa J, Howard BH, Nakatani Y, 1996. A p300/CBP-associated factor that competes with the adenoviral oncoprotein E1A. Nature. 382:319-324. [Medline]
  25. Xu W, Edmondson DG, Roth JY, 1998. Mammalian GCNS and P/CAF acetyltransferases have homologous amino-terminal domains important for recognition of nucleosomal substrates. Mol Cell Biol. 18:5659-5669. [Abstract/Free Full Text]
  26. Takayama E, Seki S, Ohkawa T, et al. 2000. Mouse CD8+ CD122+ T cells with intermediate TCR increasing with age provide a source of early IFN-gamma production. J Immunol. 164:5652-5658. [Abstract/Free Full Text]
  27. Wakikawa A, Utsuyama M, Wakabayashi A, Kitagawa M, Hirokawa K, 1999. Age-related alteration of cytokine production profile by T cell subsets in mice: a flow cytometric study. Exp Gerontol. 34:231-242. [Medline]
  28. Tanaka Y, Naruse I, Hong T, et al. 2000. Extensive brain hemorrhage and embryonic lethality in a mouse null mutant of CREB-binding protein. Mech Dev. 95:133-145. [Medline]
  29. Yao TP, Oh SP, Fuchs M, et al. 1998. Gene dosage-dependent embryonic development and proliferation defects in mice lacking the transcriptional integrator p300. Cell. 93:361-372. [Medline]
  30. Sasaki K, Matsumura G, 1987. Hemopoietic cells in the liver and spleen of the embryonic and early postnatal mouse: a karyometrical observation. Anat Rec. 219:378-383. [Medline]
  31. Corso A, Hogeweg-Platenburg MG, De Vries P, Visser JW, 1993. A protocol for the enrichment of different types of CFU-S from fetal mouse liver. Hematologica. 78:5-11.
  32. Ogryzko VV, Hirai TH, Russanova VR, Barbie DA, Howard BH, 1996. Human fibroblast commitment to a senescence-like state in response to histone deacetylase inhibitors is cell cycle dependent. Mol Cell Biol. 16:5210-5218. [Abstract]
  33. Xiao H, Hasegawa T, Miyaishi O, Ohkusu K, Isobe K, 1997. Sodium butyrate induces NIH3T3 cells to senescence-like state and enhances promoter activity of p21WAF/CIP1 in p53-independent manner. Biochem Biophys Res Commun. 237:457-460. [Medline]
  34. Xiao H, Hasegawa T, Isobe K, 2000. p300 collaborates with Sp1 and Sp3 in p21(waf1/cip1) promoter activation induced by histone deacetylase inhibitor. J Biol Chem. 275:1371-1376. [Abstract/Free Full Text]
  35. Wagner M, Brosch G, Zwerschke W, Seto E, Loidl P, Jansen-Durr P, 2001. Histone deacetylases in replicative senescence: evidence for a senescence-specific form of HDAC-2. FEBS Lett. 499:101-106. [Medline]



This article has been cited by other articles:


Home page
 Learn. Mem.Home page
A. M.M. Oliveira, M. A. Wood, C. B. McDonough, and T. Abel
Transgenic mice expressing an inhibitory truncated form of p300 exhibit long-term memory deficits
Learn. Mem., August 29, 2007; 14(9): 564 - 572.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Services
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
PubMed
Right arrow PubMed Citation

HOME ARCHIVE SEARCH TABLE OF CONTENTS