Epigenome rejuvenation: HP1β mobility as a measure of pluripotent and senescent chromatin ground states.
We measured the dynamics of an essential epigenetic modifier, HP1β, in human cells at different stages of differentiation using Fluorescence Recovery After Photobleaching (FRAP). We found that HP1β mobility is similar in human embryonic stem cells (hES) and iPS cells where it is more mobile compared to fibroblasts; HP1β is less mobile in senescent fibroblasts than in young (dividing) fibroblasts. Introduction of "reprogramming factors", Oct4, Sox2, Klf4, cMyc and Lin28, into senescent fibroblasts and measuring the changes in HP1β mobility as reprogramming proceeds shows that the mobility of HP1β in senescent cells increases and by day 9 is the same as that found in young fibroblasts. Thus the dynamics of a key epigenetic modifier can be rejuvenated without de-differentiation through an embryonic stage. Future work will test whether other aspects of cellular physiology that age can be so rejuvenated without de-differentiation.
Albert-Ludwigs-Universität Freiburg, BIOSS Centre for Biological Signalling Studies, Schänzlestrasse 18, 79104 Freiburg, Germany.
Maria
M
Manukyan
Fächerverbund Anatomie, Institut für Zell- und Neurobiologie, Charite - Universitätsmedizin, 10117 Berlin, Germany.
Prim B
PB
Singh
D021581:Active Transport, Cell Nucleus; D002454:Cell Differentiation; D002460:Cell Line; D065150:Cellular Reprogramming; D016922:Cellular Senescence / Q000235:genetics; D002843:Chromatin / Q000235:genetics* / Q000378:metabolism*; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D044127:Epigenesis, Genetic; D057890:Epigenomics; D005347:Fibroblasts / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D000090062:Kruppel-Like Factor 4; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D021381:Protein Transport
C000715593:CBX1 protein, human; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D000090266:Chromobox Protein Homolog 5