Cardiomyocytes acquire their primary specialized function (contraction) prior to exiting the cell cycle. Proliferation and differentiation must be precisely coordinated for proper cardiac morphogenesis. Here, we have investigated the complex transcriptional mechanisms employed by cardiomyocytes to coordinate antagonistic cell cycle and differentiation gene programs through the molecular dissection of the core cardiac transcription factor, MEF2. Knockdown of individual MEF2 proteins, MEF2A, C, and D, in primary neonatal cardiomyocytes resulted in radically distinct and opposite effects on cellular homeostasis and gene regulation. MEF2A and MEF2D were absolutely required for cardiomyocyte survival whereas MEF2C, despite its major role in cardiac morphogenesis and direct reprogramming, was dispensable for this process. Inhibition of MEF2A or D also resulted in the activation of cell cycle genes and downregulation of markers of terminal differentiation. In striking contrast, the regulation of cell cycle and differentiation gene programs by MEF2C were antagonistic to that of MEF2A and D. Computational analysis of regulatory regions from MEF2 isoform-dependent gene sets identified the Notch and Hedgehog signaling pathways as key determinants in coordinating MEF2 isoform-specific control of antagonistic gene programs. These results reveal that mammalian MEF2 family members have distinct transcriptional functions in cardiomyocytes, and suggest that these differences are critical for proper development and maturation of the heart. Analysis of MEF2 isoform-specific function in neonatal cardiomyocytes has yielded insight into an unexpected transcriptional regulatory mechanism by which these specialized cells utilize homologous members of a core cardiac transcription factor to coordinate cell cycle and differentiation gene programs.
from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2qxfe4R
via IFTTT
Εγγραφή σε:
Σχόλια ανάρτησης (Atom)
Δημοφιλείς αναρτήσεις
-
Publication date: Available online 4 January 2018 Source: European Journal of Radiology Author(s): Peiyao Zhang, Jing Wang, Qin Xu, Zhen...
-
BACKGROUND AND PURPOSE: Lesion load is a common biomarker in multiple sclerosis, yet it has historically shown modest association with cl...
-
Does CBD Oil Lower Blood Pressure? This article was originally published at SundayScaries." Madeline Taylor POSTED ON January 13, 20...
-
Despite widespread journal endorsement of reporting guidelines, the poor reproducibility of preclinical research is increasingly under debat...
-
The benefit of the breastfeeding has been well-established. In comparison to partial breast feeding, exclusive breastfeeding has even more b...
-
A report of the Cold Spring Harbor Laboratory/Wellcome Trust Meeting on Engineering Principles in Biology, Cambridge, UK, 14-16 October 2009...
-
Abstract We report here a microscopic tight-binding theoretical study of the dynamic dielectric response of graphene-on-polarizable substr...
-
Background Hyperthyroidism is associated with increased thrombotic risk. As contact system activation through formation of neutrophil extrac...
-
The “new” silk road—the belt and road initiative (BRI)—is China’s grand idea for the 21st century, promising to transform international deve...
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου