Marking of active genes on mitotic chromosomes

Abstract

During development and differentiation, cellular phenotypes are stably propagated through numerous cell divisions. This epigenetic 'cell memory' helps to maintain stable patterns of gene expression. DNA methylation and the propagation of specific chromatin structures may both contribute to cell memory. There are two impediments during the cell cycle that can hinder the inheritance of specific chromatin configurations: first, the pertinent structures must endure the passage of DNA-replication forks in S phase; second, the chromatin state must survive mitosis, when chromatin condenses, transcription is turned off, and almost all double-stranded DNA-binding proteins are displaced. After mitosis, the previous pattern of expressed and silent genes must be restored. This restoration might be governed by mass action, determined by the binding affinities and concentrations of individual components. Alternatively, a subset of factors might remain bound to mitotic chromosomes, providing a molecular bookmark to direct proper chromatin reassembly. Here we analyse DNA at transcription start sites during mitosis in vivo and find that it is conformationally distorted in genes scheduled for reactivation but is undistorted in repressed genes. These protein-dependent conformational perturbations could help to re-establish transcription after mitosis by 'marking' genes for re-expression.

Pioneer transcription factors in cell reprogramming

“…Although most transcription factors and RNA polymerase II dissociate from mitotic chromatin, a subset of transcription factors are retained, originally referred to as ''bookmarking'' factors (Martinez-Balbas et al 1995;Michelotti et al 1997;Zaidi et al 2010). In the time since this initial discovery, it has become appreciated that the mitotic-retaining bookmarking factors are typically those classified as pioneer transcription factors, including GATA1 and FoxA1 (Table 1; Kadauke et al 2012;Caravaca et al 2013).…”

The Y-box Binding Protein YB-1 Suppresses Collagen α1(I) Gene Transcription via an Evolutionarily Conserved Regulatory Element in the Proximal Promoter

“…Numerous single-stranded DNA-binding proteins have been identified (41)(42)(43)(44)(45), raising the question of how these proteins approach their binding motifs within the DNA. YB-1 has both double-and single-stranded DNA binding properties and, most importantly, can induce DNA strand separation (12,22,46).…”

Chromatin fine structure of the c- MYC insulator element/DNase I-hypersensitive site I is not preserved during mitosis

“…attractive scenario that could reconcile the transient disruption of preexisting complexes during mitosis and the stability of epigenetic cell memory has been suggested: only a subset of protein factors remains bound to mitotic chromosomes, and these serve as marks that then help reestablish complexes after mitosis (8)(9)(10)(11)(12)(13)(14). Although it has been proposed in ref.…”

“…It has been established that DNA methylation and histone modifications play important roles in epigenetic control (6,7). On the other hand, some recent models for mitotic cell memory assume that a subset of protein factors remains associated with previously active genes during mitosis and that these factors serve as epigenetic marks (8)(9)(10)(11)(12)(13)(14).The significance and mechanism of such protein associations are yet to be elucidated.…”