Anaphase

Mitotic exit

Transcription factor

Biology

Promoter

Gene

Enhancer

Gene expression

Philosophy

Bookmarking

Transcription (linguistics)

Molecular biology

Cell cycle

Linguistics

RNA polymerase II

Mitosis

Cell biology

Interphase

Genetics

Chromatin

Nature Reviews Molecular Cell Biology

The highly reproducible inheritance of chromosomes during mitosis in mammalian cells involves nuclear envelope breakdown, increased chromatin compaction, loss of long-range intrachromosomal interactions, loss of enhancer–promoter proximity, displacement of many transcription regulators from the chromatin and a marked decrease in RNA synthesis. Despite these dramatic changes in the mother cell, daughter cells are able to faithfully re-establish the parental chromatin and gene expression features characteristic of the cell type. Pioneering studies of mitotic chromatin signatures showed that despite global repression of transcription, the Hsp70 gene promoter retains an open chromatin conformation, which was proposed to allow the reactivation of the Hsp70 gene upon completion of mitosis — a phenomenon termed mitotic bookmarking. It was later shown that various cell-type-specific transcription factors, such as GATA-binding factor 1 (GATA1) in erythroblasts and forkhead box protein A1 (FOXA1) in hepatocytes, remain bound at a subset of their interphase binding sites in mitosis. Such bookmarking transcription factors remain on chromosomes in mitosis and have been shown to enable a subset of genes to be reactivated in a timely fashion upon mitotic exit. In addition, sensitive new methods to measure transcription revealed that mitotic cells retain residual transcription at a large number of genes. Furthermore, genes recover their interphase level of&nbsp;transcription in distinct waves. Thus, gene expression is precisely regulated as cells pass through mitosis to ensure faithful propagation of cell identity and function through cellular generations. Recent data indicate that various transcription factors and RNA polymerase II bind to mitotic chromatin and that thousands of genes remain transcriptionally active in mitosis, contradicting the view that mitotic cells are transcriptionally silenced. These mechanisms provide mitotic transcriptional memory, which allows re-establishment of cell-type-specific gene expression following division.

A changing paradigm of transcriptional memory propagation through mitosis