Dataset Information

Transcription factor activity and nucleosome organization in mitosis.

ABSTRACT: Mitotic bookmarking transcription factors (BFs) maintain the capacity to bind to their targets during mitosis, despite major rearrangements of the chromatin. While they were thought to propagate gene regulatory information through mitosis by statically occupying their DNA targets, it has recently become clear that BFs are highly dynamic in mitotic cells. This represents both a technical and a conceptual challenge to study and understand the function of BFs: First, formaldehyde has been suggested to be unable to efficiently capture these transient interactions, leading to profound contradictions in the literature; and second, if BFs are not permanently bound to their targets during mitosis, it becomes unclear how they convey regulatory information to daughter cells. Here, comparing formaldehyde to alternative fixatives we clarify the nature of the chromosomal association of previously proposed BFs in embryonic stem cells: While ESRRB can be considered as a canonical BF that binds at selected regulatory regions in mitosis, SOX2 and POU5F1 (also known as OCT4) establish DNA sequence-independent interactions with the mitotic chromosomes, either throughout the chromosomal arms (SOX2) or at pericentromeric regions (POU5F1). Moreover, we show that ordered nucleosomal arrays are retained during mitosis at ESRRB bookmarked sites, whereas regions losing transcription factor binding display a profound loss of order. By maintaining nucleosome positioning during mitosis, ESRRB might ensure the rapid post-mitotic re-establishment of functional regulatory complexes at selected enhancers and promoters. Our results provide a mechanistic framework that reconciles dynamic mitotic binding with the transmission of gene regulatory information across cell division.

SUBMITTER: Festuccia N

PROVIDER: S-EPMC6360816 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Transcription factor activity and nucleosome organization in mitosis.

Festuccia Nicola N Owens Nick N Papadopoulou Thaleia T Gonzalez Inma I Tachtsidi Alexandra A Vandoermel-Pournin Sandrine S Gallego Elena E Gutierrez Nancy N Dubois Agnès A Cohen-Tannoudji Michel M Navarro Pablo P

Genome research 20190117 2

Mitotic bookmarking transcription factors (BFs) maintain the capacity to bind to their targets during mitosis, despite major rearrangements of the chromatin. While they were thought to propagate gene regulatory information through mitosis by statically occupying their DNA targets, it has recently become clear that BFs are highly dynamic in mitotic cells. This represents both a technical and a conceptual challenge to study and understand the function of BFs: First, formaldehyde has been suggested ...[more]

PMID: 30655337

Similar Datasets

Project description:BackgroundThe binding of transcription factors (TFs) to specific DNA sequences is an initial and crucial step of transcription. In eukaryotes, this process is highly dependent on the local chromatin state, which can be modified by recruiting chromatin remodelers. However, previous studies have focused mainly on nucleosome occupancy around the TF binding sites (TFBSs) of a few specific TFs. Here, we investigated the nucleosome occupancy profiles around computationally inferred binding sites, based on 519 TF binding motifs, in human GM12878 and K562 cells.ResultsAlthough high nucleosome occupancy is intrinsically encoded at TFBSs in vitro, nucleosomes are generally depleted at TFBSs in vivo, and approximately a quarter of TFBSs showed well-positioned in vivo nucleosomes on both sides. RNA polymerase near the transcription start site (TSS) has a large effect on the nucleosome occupancy distribution around the binding sites located within one kilobase to the nearest TSS; fuzzier nucleosome positioning was thus observed around these sites. In addition, in contrast to yeast, repressors, rather than activators, were more likely to bind to nucleosomal DNA in the human cells, and nucleosomes around repressor sites were better positioned in vivo. Genes with repressor sites exhibiting well-positioned nucleosomes on both sides, and genes with activator sites occupied by nucleosomes had significantly lower expression, suggesting that actions of activators and repressors are associated with the nucleosome occupancy around their binding sites. It was also interesting to note that most of the binding sites, which were not in the DNase I-hypersensitive regions, were cell-type specific, and higher in vivo nucleosome occupancy were observed at these binding sites.ConclusionsThis study demonstrated that RNA polymerase and the functions of bound TFs affected the local nucleosome occupancy around TFBSs, and nucleosome occupancy patterns around TFBSs were associated with the expression levels of target genes.

Dataset Information

Transcription factor activity and nucleosome organization in mitosis.

Publications

Transcription factor activity and nucleosome organization in mitosis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets