We report here that ESCL protein exhibits
We report here that ESCL protein exhibits a temporal expression profile that is complementary to that of ESC, including substantially higher levels of expression during larval and adult stages than embryogenesis. We show that ESCL, like ESC, binds directly to E(Z) via its WD repeats and is physically associated with E(Z), SU(Z)12, PCL and p55 in vivo. While RNAi-mediated knockdown of either ESC or ESCL in S2 cells has no appreciable effect on histone H3K27 methylation, simultaneous knockdown of both strongly reduces tri-methyl and di-methyl (3m and 2m) H3K27 levels. Some ESCL is bound to the Ubx PRE in Drosophila Kc cells and this binding is increased when ESC is depleted by RNAi. A strong escl mutation is viable and fertile but enhances the phenotypes of PcG mutants, consistent with a role in Polycomb silencing. Genetic analysis reveals that the well-known “maternal rescue” of esc− embryos to viable adults requires ESCL. GAL4-driven constitutive maternal and zygotic ESCL expression can fully substitute for ESC in vivo, indicating that their functions are qualitatively indistinguishable if not identical. We discuss why two apparently functionally equivalent proteins have been retained during Drosophila evolution.
Materials and methods
Acknowledgments We thank previous and current members of Harte lab, especially Takehito Furuyama, Tom Breen, Rakhee Banerjee and Vincent Stepanik for their advice. Rabbit Dihydro-β-erythroidine hydrobromide molecular that specifically recognize trimethyl H3K27 were generously provided by Dr. Thomas Jenuwein. S2 cells (serum-dependent) and escl cDNAs were obtained from the Drosophila Genomics Resource Center. This work was supported by a grant (GM39255) from the National Institutes of Health to PJH and by an NIH predoctoral Training Grant award (T32HD007104) to RLK.
Introduction Although the increased risk of cardiovascular disease due to arterial hypertension is a notion recognized since the introduction of blood pressure (BP) devices, the benefits of BP lowering have been increasingly accepted starting from the last five decades , since the publication of major randomized clinical trials including hundreds of thousands of hypertensive individuals. The ultimate goal of anti-hypertensive treatment is the reduction and, ideally, the abolition of the excess of cardiovascular mortality and morbidity related to chronically elevated BP. In this perspective, tight BP control in hypertensive patients is crucial to ensure optimal protection against cardiovascular complications. Over the past 20 years, major international guidelines of hypertension management have been recommending that optimal treatment of hypertensive patients should be based not exclusively on BP levels, but also on the precise assessment of individual total cardiovascular risk , , , . These recommendations have been supported by increasing evidence that only a limited fraction of the hypertensive population is affected by BP elevation alone, a large fraction presenting concurrent non-modifiable and modifiable cardiovascular risk factors. The latest 2013 ESH/ESC Guidelines recommend a simple flow-chart for estimating the combined effect of various risk factors, target organ damage and comorbidities on global risk of fatal cardiovascular events . Estimates take into account systolic and/or diastolic BP levels, coexistence of modifiable (smoking, dyslipidaemia, glucose intolerance, obesity) and non-modifiable (male sex, age and family history of premature cardiovascular disease) risk factors, signs of cardiac and extra-cardiac target organ damage, evidence of diabetes mellitus and established cardiovascular or renal disease. This approach allows to classify hypertensive patients at low, moderate, high and very high risk according to 10-year risk of cardiovascular mortality as suggested by 2012 ESC prevention guidelines . This article is a review of the recommendations provided by the ESH/ESC guidelines  on a number of issues related to treatment of hypertension: 1) BP targets; 2) life-style changes, 3) pharmacological therapy (general principles, anti-hypertensive treatment in special clinical settings).