Interaction between Acetylated MyoD and the Bromodomain of CBP and/or p300

Polesskaya, Anna; Naguibneva, Irina; Duquet, Arnaud; Bengal, Eyal; Robin, Philippe; Harel‐Bellan, Annick

doi:10.1128/mcb.21.16.5312-5320.2001

Cited by 94 publications

(69 citation statements)

References 44 publications

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“…Consistent with previous studies demonstrating that p300 and pCAF were coactivators of MyoD (7,8,11,12,27), we observed that both of these ATs are necessary for maximal levels of transcriptional activation. Although pCAF was not sufficient for MyoD-dependent transcription, when p300 was also present, the two coactivators synergize, leading to a strong activation of transcription.…”

Section: Discussionsupporting

confidence: 81%

“…Thus, pCAF is probably recruited to the MyoD-bound promoter by means of p300, and this recruitment might be facilitated and͞or stabilized by the interaction between the bromodomain of pCAF and the acetylated histone H3 tail within the nucleosomes (9). Once stably associated with the promoter, pCAF then acetylates MyoD (11), which in turn could stabilize the interaction between MyoD and p300 (27) or aid in the recruitment of other bromodomain containing coactivators (28). Stable interaction between MyoD and p300 would facilitate the recruitment of the RNA Pol II transcriptional machinery by means of its ability to interact with the RNA Helicase A (29).…”

Section: Discussionmentioning

confidence: 99%

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In vitro transcription system delineates the distinct roles of the coactivators pCAF and p300 during MyoD/E47-dependent transactivation

Dilworth

Seaver

Fishburn

et al. 2004

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

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The transcriptional coactivators p300 and pCAF are necessary for the myogenic factor MyoD to initiate the expression of skeletal muscle genes. In addition to mediating histone acetylation, both of these factors can acetylate MyoD; however, the complexity of cellular systems used to study MyoD has impeded delineation of the specific roles of these two acetyltransferases. Therefore, we established a MyoD-dependent in vitro transcription system that permits us to determine the roles of p300 and pCAF during MyoD-dependent transcriptional activation. Consistent with results from cellular systems, we demonstrate that maximal levels of transactivation in vitro require both p300 and pCAF, as well as the cofactor acetyl CoA. Dissection of the steps leading to transcription initiation revealed that the activities of p300 and pCAF are not redundant. During the initial stages of transactivation, p300 acetylates histone H3 and H4 within the promoter region and then recruits pCAF to MyoD. Once tethered to the promoter, pCAF acetylates MyoD to facilitate the transactivation process. Thus, we have established that pCAF and p300 carry out sequential and functionally distinct events on a promoter leading to transcriptional activation. Further dissection of this in vitro transcription system should be highly useful toward elucidating the mechanism by which coactivators facilitate differential gene expression by MyoD.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

In vitro transcription system delineates the distinct roles of the coactivators pCAF and p300 during MyoD/E47-dependent transactivation

Dilworth

Seaver

Fishburn

et al. 2004

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

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“…However, this activation was reduced to 12.5-fold when STAT3-C was cotransfected, indicating that STAT3-C suppresses transcriptional activities of MyoD. Because transcriptional activities of MyoD are crucially regulated by p300, CBP, and/or PCAF through the acetylation (37,40,41), we examined the effects of these molecules on MyoD activities suppressed by STAT3. As a result, we found that the supplement of p300, CBP, and PCAF individually restored MyoD activities suppressed by STAT3 (Fig.…”

Section: Reciprocal Inhibition Between Myod and Stat3 44184mentioning

confidence: 99%

Reciprocal Inhibition between MyoD and STAT3 in the Regulation of Growth and Differentiation of Myoblasts

Kataoka

Matsumura

Ezoe

et al. 2003

Journal of Biological Chemistry

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The development of myoblasts is regulated by various growth factors as well as by intrinsic muscle-specific transcriptional factors. In this study, we analyzed the roles for STAT3 in the growth and differentiation of myoblasts in terms of cell cycle regulation and interaction with MyoD using C2C12 cells. Here we found that STAT3 inhibited myogenic differentiation induced by low serum or MyoD as efficiently as the Ras/mitogenactivated protein kinase cascade. As for this mechanism, we found that STAT3 not only promoted cell cycle progression through the induction of c-myc but also inhibited MyoD activities through direct interaction. STAT3 inhibited not only DNA binding activities of MyoD but also its transcriptional activities. However, the inhibited transcriptional activities were restored by the supplement of p300/CBP and PCAF, suggesting that STAT3 might deprive MyoD of these transcriptional cofactors. In addition, we found that MyoD inhibited DNA binding activities of STAT3, thereby inhibiting STAT3-dependent cell growth and survival of Ba/F3 cells. These results suggest that the development of muscle cells is regulated by the coordination of cytokine signals and intrinsic transcription factors.

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“…In addition, the myogenic basic helix-loop-helix protein MyoD is also acetylated in myogenic cells (12). MyoD acetylation increases its transcriptional activity by influencing its ability to bind DNA (13) and to interact with other proteins (11). In vitro, MyoD is acetylated by PCAF (13).…”

mentioning

confidence: 96%

“…HATs are involved at different steps of the differentiation program; differentiation triggers the acetylation of histones on muscle-specific promoters (11). In addition, the myogenic basic helix-loop-helix protein MyoD is also acetylated in myogenic cells (12).…”

mentioning

confidence: 99%

Acetylation of MyoD by p300 Requires More Than Its Histone Acetyltransferase Domain

Polesskaya¹,

Harel‐Bellan

2001

Journal of Biological Chemistry

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MyoD, an essential transcription factor involved in muscle cell terminal differentiation, is regulated by acetylation, as are a number of other transcription factors, but the histone acetyltransferase enzyme responsible for this acetylation is a matter of controversy. In particular, contradictory findings have been reported concerning the ability of CBP/p300 to acetylate MyoD in vitro. Here we provide an explanation for this discrepancy: although full-length p300 does indeed acetylate MyoD, a fragment of p300 corresponding to its histone acetyltransferase domain does not. In addition to clearly demonstrating that p300 acetylates MyoD in vitro, these results underscore the necessity of using full-length histone acetyltransferase enzymes to draw valid conclusions from acetylation experiments.Acetylation has recently emerged as a central mode of regulation for proteins. Histone acetyltransferases (HATs), 1 which are able to acetylate histone and non-histone proteins, are involved in a variety of essential cellular processes such as muscle-cell terminal differentiation. Muscle-cell terminal differentiation involves several families of transcription factors, including myogenic basic helix-loop-helices (MyoD, Myf-5, myogenin, and MRF-4) (1), and transcriptional co-regulators with histone acetyltransferase activity, the PCAF/GCN5 family (2-4) and the CBP/p300 family (5, 6). PCAF (7) and CBP/p300 (8, 9) are found in the same complexes (7), although they acetylate distinct targets (10).HATs are involved at different steps of the differentiation program; differentiation triggers the acetylation of histones on muscle-specific promoters (11). In addition, the myogenic basic helix-loop-helix protein MyoD is also acetylated in myogenic cells (12). MyoD acetylation increases its transcriptional activity by influencing its ability to bind DNA (13) and to interact with other proteins (11). In vitro, MyoD is acetylated by PCAF (13). Acetylation of MyoD by CBP/p300, on the other hand, has been somewhat controversial. We reported that MyoD is acetylated by CBP or p300 with an efficiency similar to that observed with PCAF (12); in contrast, others have concluded from similar experiments that MyoD is acetylated by PCAF and not by p300 in vitro (14). The latter study relied on a truncated version of the p300 protein (from amino acid 965 to amino acid 1810) that is often employed in this type of study. It is of note that the p300 965-1810 fragment has lost the main protein-protein interaction domains of p300. In particular, the regions of p300 previously shown to interact with MyoD, the CH3 domain (amino acids 1620 -1891) (15) and the N-terminal KIX domain (amino acids 379 -654) (16), are truncated or altogether deleted in p300 . Thus a possible explanation for the discrepancy between these two series of experiments might be that a physical contact between the HAT and its substrate is required for acetylation and that the interaction domains are critical for the reaction to take place. Here, we present the results of a direct test of ...

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Interaction between Acetylated MyoD and the Bromodomain of CBP and/or p300

Cited by 94 publications

References 44 publications

In vitro transcription system delineates the distinct roles of the coactivators pCAF and p300 during MyoD/E47-dependent transactivation

In vitro transcription system delineates the distinct roles of the coactivators pCAF and p300 during MyoD/E47-dependent transactivation

Reciprocal Inhibition between MyoD and STAT3 in the Regulation of Growth and Differentiation of Myoblasts

Acetylation of MyoD by p300 Requires More Than Its Histone Acetyltransferase Domain

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