Regulation of PCAF Activity by Spermidine

Risultato della ricerca: Other

Abstract

Histones and polyamines are important determinants of chromatin structure. Histones are the core of nucleosome particles and their modification by acetylation of N-terminal tails is involved in chromatin structural changes and transcriptional modulation. Polyamines also, including spermidine, are targets of both nuclear and cytoplasmic acetylation, which in turn alters their affinity for DNA and nucleosomes. Previous studies report an interplay existing between polyamines metabolism and levels, and histone acetylation. The relationship between polyamines and histone epigenetics in vivo has been considered in various models of ageing through epigenetic modifications, induction of autophagy and suppression of necrosis, but the molecular basis of this effect is still unclear.In order to gain new insights on the mechanism by which spermidine is able to induce histone hypoacetylation in vivo, we monitored for the first time the in vitro effect of spermidine on H3 acetylation catalyzed by PCAF, a highly conserved histone acetyltrasferase (HAT). Interestingly, we found a specific inhibitory effect of spermidine in a broad range of concentration. However, we observed the opposite effect at very low spermidine concentrations, revealing an intriguing bimodal effect of spermidine on histone acetylation, depending exquisitely on its concentration. Moreover, we demonstrated for the first time the involvement of PCAF in the modification of spermidine to N8-acetylspermidine, which in turn might regulate the catalitic activity of PCAF itself.
Lingua originaleEnglish
Pagine47-47
Numero di pagine65
Stato di pubblicazionePublished - 2011

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Spermidine
Histones
Acetylation
Polyamines
Nucleosomes
Epigenomics
Chromatin
Autophagy
Necrosis
DNA

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title = "Regulation of PCAF Activity by Spermidine",
abstract = "Histones and polyamines are important determinants of chromatin structure. Histones are the core of nucleosome particles and their modification by acetylation of N-terminal tails is involved in chromatin structural changes and transcriptional modulation. Polyamines also, including spermidine, are targets of both nuclear and cytoplasmic acetylation, which in turn alters their affinity for DNA and nucleosomes. Previous studies report an interplay existing between polyamines metabolism and levels, and histone acetylation. The relationship between polyamines and histone epigenetics in vivo has been considered in various models of ageing through epigenetic modifications, induction of autophagy and suppression of necrosis, but the molecular basis of this effect is still unclear.In order to gain new insights on the mechanism by which spermidine is able to induce histone hypoacetylation in vivo, we monitored for the first time the in vitro effect of spermidine on H3 acetylation catalyzed by PCAF, a highly conserved histone acetyltrasferase (HAT). Interestingly, we found a specific inhibitory effect of spermidine in a broad range of concentration. However, we observed the opposite effect at very low spermidine concentrations, revealing an intriguing bimodal effect of spermidine on histone acetylation, depending exquisitely on its concentration. Moreover, we demonstrated for the first time the involvement of PCAF in the modification of spermidine to N8-acetylspermidine, which in turn might regulate the catalitic activity of PCAF itself.",
keywords = "Acetylspermidine, Histones, PCAF, Spermidine",
author = "Gennaro Taibi and Giosalba Burgio",
year = "2011",
language = "English",
pages = "47--47",

}

TY - CONF

T1 - Regulation of PCAF Activity by Spermidine

AU - Taibi, Gennaro

AU - Burgio, Giosalba

PY - 2011

Y1 - 2011

N2 - Histones and polyamines are important determinants of chromatin structure. Histones are the core of nucleosome particles and their modification by acetylation of N-terminal tails is involved in chromatin structural changes and transcriptional modulation. Polyamines also, including spermidine, are targets of both nuclear and cytoplasmic acetylation, which in turn alters their affinity for DNA and nucleosomes. Previous studies report an interplay existing between polyamines metabolism and levels, and histone acetylation. The relationship between polyamines and histone epigenetics in vivo has been considered in various models of ageing through epigenetic modifications, induction of autophagy and suppression of necrosis, but the molecular basis of this effect is still unclear.In order to gain new insights on the mechanism by which spermidine is able to induce histone hypoacetylation in vivo, we monitored for the first time the in vitro effect of spermidine on H3 acetylation catalyzed by PCAF, a highly conserved histone acetyltrasferase (HAT). Interestingly, we found a specific inhibitory effect of spermidine in a broad range of concentration. However, we observed the opposite effect at very low spermidine concentrations, revealing an intriguing bimodal effect of spermidine on histone acetylation, depending exquisitely on its concentration. Moreover, we demonstrated for the first time the involvement of PCAF in the modification of spermidine to N8-acetylspermidine, which in turn might regulate the catalitic activity of PCAF itself.

AB - Histones and polyamines are important determinants of chromatin structure. Histones are the core of nucleosome particles and their modification by acetylation of N-terminal tails is involved in chromatin structural changes and transcriptional modulation. Polyamines also, including spermidine, are targets of both nuclear and cytoplasmic acetylation, which in turn alters their affinity for DNA and nucleosomes. Previous studies report an interplay existing between polyamines metabolism and levels, and histone acetylation. The relationship between polyamines and histone epigenetics in vivo has been considered in various models of ageing through epigenetic modifications, induction of autophagy and suppression of necrosis, but the molecular basis of this effect is still unclear.In order to gain new insights on the mechanism by which spermidine is able to induce histone hypoacetylation in vivo, we monitored for the first time the in vitro effect of spermidine on H3 acetylation catalyzed by PCAF, a highly conserved histone acetyltrasferase (HAT). Interestingly, we found a specific inhibitory effect of spermidine in a broad range of concentration. However, we observed the opposite effect at very low spermidine concentrations, revealing an intriguing bimodal effect of spermidine on histone acetylation, depending exquisitely on its concentration. Moreover, we demonstrated for the first time the involvement of PCAF in the modification of spermidine to N8-acetylspermidine, which in turn might regulate the catalitic activity of PCAF itself.

KW - Acetylspermidine

KW - Histones

KW - PCAF

KW - Spermidine

UR - http://hdl.handle.net/10447/60374

M3 - Other

SP - 47

EP - 47

ER -