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Control of histone H3 phosphorylation by CaMKIIδ in response to haemodynamic cardiac stress.

Awad S, Al-Haffar KM, Marashly Q, Quijada P, Kunhi M, Al-Yacoub N, Wade FS, Mohammed SF, Al-Dayel F, Sutherland G, Assiri A, Sussman M, Bers D, Al-Habeeb W, Poizat C - J. Pathol. (2014)

Bottom Line: Heart failure is associated with the reactivation of a fetal cardiac gene programme that has become a hallmark of cardiac hypertrophy and maladaptive ventricular remodelling, yet the mechanisms that regulate this transcriptional reprogramming are not fully understood.Similar changes are detected in patients with end-stage heart failure, where CaMKIIδ specifically interacts with phospho-H3.The findings reveal a novel in vivo function of CaMKIIδ in regulating H3 phosphorylation and suggest a novel epigenetic mechanism by which CaMKIIδ controls cardiac hypertrophy.

View Article: PubMed Central - PubMed

Affiliation: Cardiovascular Research Programme, King Faisal Specialist Hospital and Research Centre, Riyadh, Kingdom of Saudi Arabia.

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Related in: MedlinePlus

Hypothetical model showing the regulation of H3 phosphorylation by CaMKIIδ in response to haemodynamic stress. Pressure overload hypertrophy increases CaMKIIδ, which is subsequently recruited to chromatin regions to phosphorylate H3 at S10. H3 hyperphosphorylation relaxes chromatin, allowing binding of 14–3–3 and recruitment of transcription factors (ie GATA-4, Mef2) to promote transcriptional elongation of hypertrophic genes by RNAPII
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fig07: Hypothetical model showing the regulation of H3 phosphorylation by CaMKIIδ in response to haemodynamic stress. Pressure overload hypertrophy increases CaMKIIδ, which is subsequently recruited to chromatin regions to phosphorylate H3 at S10. H3 hyperphosphorylation relaxes chromatin, allowing binding of 14–3–3 and recruitment of transcription factors (ie GATA-4, Mef2) to promote transcriptional elongation of hypertrophic genes by RNAPII

Mentions: CaMKII enzyme is central to pathological hypertrophic pathways, structural heart disease, arrhythmia and diabetes [19–22,31,32]. We recently reported that in isolated cells, CaMKIIδ interacts with H3 to increase p-H3 S10, and that the S10 site is critical for chromatin-dependent transcription of Mef2 [25]. In the present study, we show that H3 phosphorylation is regulated by CaMKIIδ in vivo, and that this modification controls fetal cardiac gene expression in response to pressure overload. Mechanistically, fetal cardiac genes are activated by binding of 14–3–3 to phosphorylated H3, which facilitates the transcription elongation by RNAPII (Figure 7).


Control of histone H3 phosphorylation by CaMKIIδ in response to haemodynamic cardiac stress.

Awad S, Al-Haffar KM, Marashly Q, Quijada P, Kunhi M, Al-Yacoub N, Wade FS, Mohammed SF, Al-Dayel F, Sutherland G, Assiri A, Sussman M, Bers D, Al-Habeeb W, Poizat C - J. Pathol. (2014)

Hypothetical model showing the regulation of H3 phosphorylation by CaMKIIδ in response to haemodynamic stress. Pressure overload hypertrophy increases CaMKIIδ, which is subsequently recruited to chromatin regions to phosphorylate H3 at S10. H3 hyperphosphorylation relaxes chromatin, allowing binding of 14–3–3 and recruitment of transcription factors (ie GATA-4, Mef2) to promote transcriptional elongation of hypertrophic genes by RNAPII
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4383650&req=5

fig07: Hypothetical model showing the regulation of H3 phosphorylation by CaMKIIδ in response to haemodynamic stress. Pressure overload hypertrophy increases CaMKIIδ, which is subsequently recruited to chromatin regions to phosphorylate H3 at S10. H3 hyperphosphorylation relaxes chromatin, allowing binding of 14–3–3 and recruitment of transcription factors (ie GATA-4, Mef2) to promote transcriptional elongation of hypertrophic genes by RNAPII
Mentions: CaMKII enzyme is central to pathological hypertrophic pathways, structural heart disease, arrhythmia and diabetes [19–22,31,32]. We recently reported that in isolated cells, CaMKIIδ interacts with H3 to increase p-H3 S10, and that the S10 site is critical for chromatin-dependent transcription of Mef2 [25]. In the present study, we show that H3 phosphorylation is regulated by CaMKIIδ in vivo, and that this modification controls fetal cardiac gene expression in response to pressure overload. Mechanistically, fetal cardiac genes are activated by binding of 14–3–3 to phosphorylated H3, which facilitates the transcription elongation by RNAPII (Figure 7).

Bottom Line: Heart failure is associated with the reactivation of a fetal cardiac gene programme that has become a hallmark of cardiac hypertrophy and maladaptive ventricular remodelling, yet the mechanisms that regulate this transcriptional reprogramming are not fully understood.Similar changes are detected in patients with end-stage heart failure, where CaMKIIδ specifically interacts with phospho-H3.The findings reveal a novel in vivo function of CaMKIIδ in regulating H3 phosphorylation and suggest a novel epigenetic mechanism by which CaMKIIδ controls cardiac hypertrophy.

View Article: PubMed Central - PubMed

Affiliation: Cardiovascular Research Programme, King Faisal Specialist Hospital and Research Centre, Riyadh, Kingdom of Saudi Arabia.

Show MeSH
Related in: MedlinePlus