Mitotic Bookmarking: Maintaining Post-Mitotic Reprogramming of Transcription Reactivation

Abstract

Restoring chromatin structure with high fidelity after mitosis is critical for cell survival. Transcriptional reactivation of genes is the first step toward establishing identity of the daughter cell. During mitosis, chromatin bookmarking factors associated with specific chromatin regions ensure the restoration of the original gene expression pattern in daughter cells. Recent findings have provided new insights into the mechanisms, regulation, and biological significance of gene bookmarking in eukaryotes. In this review, we discuss how epigenetic factors, such as Poly(ADP-ribose) Polymerase-1, establish epigenetic memory in mitotic chromatin.

A dynamic mode of mitotic bookmarking by transcription factors

“…Several mechanisms have been proposed to play important roles in re-establishing transcription following mitosis (Lodhi et al, 2016). These include maintenance of DNA methylation patterns for heritable silencing and the propagation of histone modifications, although a model to account for targeted modifications in the absence of TFs has been elusive.…”

“…It was therefore a significant step in resolving this conundrum when HSF2 was shown to bind at the hsp70i locus during mitosis (Xing et al, 2005). Since then, and coincident with the advent of live-cell microscopy, a few other TFs have been discovered to associate with mitotic chromosomes (Caravaca et al, 2013; Kadauke et al, 2012; Lodhi et al, 2016), beginning a re-emergence of an appreciation for TFs in propagating transcription programs through mitosis. For instance, GATA1, a major regulator of the erythroid lineage, has previously been reported to be excluded from mitotic chromosomes by immunofluorescence (Xin et al, 2007).…”

Mitotic Gene Bookmarking: An Epigenetic Mechanism for Coordination of Lineage Commitment, Cell Identity and Cell Growth

“…In 2003, our group identified the osteogenic master regulator RUNX2 as the first sequence specific bookmark that remained associated with target genes through mitosis (Zaidi et al 2003). Subsequent studies of RUNX family of phenotypic transcription factors from our group (Zaidi et al 2003;Young et al 2007a;Young et al 2007b;Ali et al 2008;Bakshi et al 2008;Pande et al 2009;Ali et al 2010;Zaidi et al 2010;Ali et al 2012;Zaidi et al 2014;Lopez-Camacho et al 2014) and studies by other groups examining various transcription factors (Xing 2005;Sarge and Park-Sarge 2005;Dey et al 2009;Blobel et al 2009;Zhao et al 2011;Kadauke et al 2012;Arampatzi et al 2013;Caravaca et al 2013;Kadauke and Blobel 2013;Lake et al 2014;Zaret 2014;Lodhi et al 2014;Wong et al 2014;Lodhi et al 2016;Lerner et al 2016;Festuccia et al 2016) have identified mitotic bookmarking as a key epigenetic mechanism for regulation of genes that coordinate cell growth and lineage maintenance following mitosis.…”

“…Ali et al 2008;Bakshi et al 2008;Pande et al 2009;Dey et al 2009;Blobel et al 2009;Ali et al 2010;Zaidi et al 2010;Zhao et al 2011;Ali et al 2012;Kadauke et al 2012;Arampatzi et al 2013;Caravaca et al 2013;Kadauke and Blobel 2013;Zaidi et al 2014;Lake et al 2014;Zaret 2014;Lodhi et al 2014;Wong et al 2014;Lopez-Camacho et al 2014;Lodhi et al 2016;Lerner et al 2016;Festuccia et al 2016). Each of these transcription factors occupy a subset of their target genes during mitosis in their respective lineages.…”

Bivalent Epigenetic Control of Oncofetal Gene Expression in Cancer

“…Within a given cell, there are many distinct carriers of epigenetic information that are relayed to progeny upon cell division. Epigenetic mechanisms include methylation of CpG residues, modifications of nucleosomal histone proteins, regulation of gene transcription and protein translation by noncoding RNA molecules, and mitotic retention of transcription factors (1)(2)(3)(4)(5)(6)(7)(8). From an architectural perspective, epigenetic control is engaged at multiple levels of nuclear organization from sequence-specific regulatory elements to chromatin remodeling at the nucleosomal level to large-scale inter-and intrachromosomal interactions (9)(10)(11)(12)(13)(14).…”