title: Characterisation and regulation of E2F-6 and E2F-6b in the rat heart: a potential target for myocardial regeneration?
abstract: The E2F transcription factors are instrumental in regulating cell cycle progression and growth, including that in cardiomyocytes, which exit the cell cycle shortly after birth. E2F-6 has been demonstrated to act as a transcriptional repressor; however, its potential role in normal cardiomyocyte proliferation and hypertrophy has not previously been investigated. Here we report the isolation and characterisation of E2F-6 and E2F-6b in rat cardiomyocytes and consider its potential as a target for myocardial regeneration following injury. At the mRNA level, both rat E2F-6 and the alternatively spliced variant, E2F-6b, were expressed in E18 myocytes and levels were maintained throughout development into adulthood. Interestingly, E2F-6 protein expression was down-regulated during myocyte development suggesting that it is regulated post-transcriptionally in these cells. During myocyte hypertrophy, the mRNA expressions of E2F-6 and E2F-6b were not regulated whereas E2F-6 protein was up-regulated significantly. Indeed, E2F-6 protein expression levels closely parallel the developmental withdrawal of myocytes from the cell cycle and the subsequent reactivation of their cell cycle machinery during hypertrophic growth. Furthermore, depletion of E2F-6, using anti-sense technology, results in death of cultured neonatal myocytes. Taken together, abrogation of E2F-6 expression in neonatal cardiomyocytes leads to a significant decrease in their viability, consistent with the notion that E2F-6 might be required for maintaining normal myocyte growth.
authors.affiliation: Department of Oncology, Hutchison/MRC Research Centre, University of Cambridge, Addenbrookes Hospital, Cambridgeshire, CB2 2XZ, UK.
authors.forename: Mehregan
authors.initials: M
authors.lastname: Movassagh
authors.forename: Katrina A
authors.initials: KA
authors.lastname: Bicknell
authors.forename: Gavin
authors.initials: G
authors.lastname: Brooks
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D002453:Cell Cycle; D002470:Cell Survival; D002478:Cells, Cultured; D050701:E2F6 Transcription Factor / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D005333:Fetus; D005786:Gene Expression Regulation; D006352:Heart Ventricles; D008297:Male; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000502:physiology; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012038:Regeneration / Q000235:genetics; D016415:Sequence Alignment; D014162:Transfection
chemical_list: D050701:E2F6 Transcription Factor; D012333:RNA, Messenger