The "occlusis" model of cell fate restriction.
A simple model, termed "occlusis", is presented here to account for both cell fate restriction during somatic development and reestablishment of pluripotency during reproduction. The model makes three assertions: (1) A gene's transcriptional potential can assume one of two states: the "competent" state, wherein the gene is responsive to, and can be activated by, trans-acting factors in the cellular milieu, and the "occluded" state, wherein the gene is blocked by cis-acting, chromatin-based mechanisms from responding to trans-acting factors such that it remains silent irrespective of whether transcriptional activators are present in the milieu. (2) As differentiation proceeds in somatic lineages, lineage-inappropriate genes shift progressively and irreversibly from competent to occluded state, thereby leading to the restriction of cell fate. (3) During reproduction, global deocclusion takes place in the germline and/or early zygotic cells to reset the genome to the competent state in order to facilitate a new round of organismal development.
Department of Human Genetics, Howard Hughes Medical Institute, University of Chicago, Chicago, IL, USA. blahn@bsd.uchicago.edu
Bruce T
BT
Lahn
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D048708:Cell Growth Processes; D002843:Chromatin / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D020868:Gene Silencing; D016678:Genome; D006801:Humans; D008954:Models, Biological; D039904:Pluripotent Stem Cells / Q000502:physiology; D012098:Reproduction; D015534:Trans-Activators / Q000235:genetics*; D014158:Transcription, Genetic / Q000502:physiology*; D015533:Transcriptional Activation
D002843:Chromatin; D015534:Trans-Activators