Bookmarking (also "gene bookmarking" or "mitotic bookmarking") refers to a potential mechanism of transmission of gene expression programs through cell division. During

mitosis Mitosis () is a part of the cell cycle in eukaryote, eukaryotic cells in which replicated chromosomes are separated into two new Cell nucleus, nuclei. Cell division by mitosis is an equational division which gives rise to genetically identic ...

gene transcription Transcription is the process of copying a segment of DNA into RNA for the purpose of gene expression. Some segments of DNA are transcribed into RNA molecules that can encode proteins, called messenger RNA (mRNA). Other segments of DNA are transc ...

is silenced and most

transcription factors In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The fun ...

are removed from

chromatin Chromatin is a complex of DNA and protein found in eukaryote, eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important r ...

. The term bookmarking compares transcription to reading from a book. The pause in transcription during mitosis is like closing the book. "Molecular bookmarks" are the factors that allow transcription to resume in an orderly fashion in newborn cells following mitosis (when the book is re-opened). Bookmarks fulfill the following criteria: * at some point prior to the onset of

, the promoters of genes that exist in a transcription-competent state become "marked" in some way, * this "mark" persists both during and after

, and * the marking transmits gene expression memory by preventing the mitotic compaction of DNA at this locus, or by facilitating reassembly of transcription complexes on the promoter, or both.

Bookmarking as selective maintenance of an open chromatin state

The term bookmarking was originally coined to describe the non-compaction of some

gene promoter In genetics, a promoter is a sequence of DNA to which proteins bind to initiate transcription (genetics), transcription of a single RNA transcript from the DNA downstream of the promoter. The RNA transcript may encode a protein (mRNA), or can hav ...

s during

. More recently genome accessibility during interphase and mitosis has been directly compared on a genome-wide scale. While gene promoters tend to be better preserved than distal regulatory elements, substantial variation exists at individual sites.

Bookmarking by DNA methylation, histone post-translation modification, and histone variants

Some patterns of

histone In biology, histones are highly basic proteins abundant in lysine and arginine residues that are found in eukaryotic cell nuclei and in most Archaeal phyla. They act as spools around which DNA winds to create structural units called nucleosomes ...

modification and the presence of some histone variants on DNA remain unchanged during mitosis and have the potential to act as bookmarks. Patterns of

DNA methylation DNA methylation is a biological process by which methyl groups are added to the DNA molecule. Methylation can change the activity of a DNA segment without changing the sequence. When located in a gene promoter (genetics), promoter, DNA methylati ...

are generally unchanged and also have the potential to function as bookmarks.

Bookmarking by transcription factors

Notable transcription factors implicated in mitotic bookmarking include: *

BRD4 Bromodomain-containing protein 4 is a protein that in humans is encoded by the ''BRD4'' gene. BRD4 is a member of the BET (bromodomain and extra terminal domain) family, which also includes BRD2, BRD3, and BRDT. BRD4, similar to other BET fam ...

GATA1 GATA-binding factor 1 or GATA-1 (also termed Erythroid transcription factor) is the founding member of the GATA family of transcription factors. This protein is widely expressed throughout vertebrate species. In humans and mice, it is encoded b ...

HSP70 The 70 kilodalton heat shock proteins (Hsp70s or DnaK) are a family of conserved ubiquitously expressed heat shock proteins. Proteins with similar structure exist in virtually all living organisms and play crucial roles in the development of can ...

TFIID Transcription factor II D (TFIID) is one of several general transcription factors that make up the RNA polymerase II preinitiation complex. RNA polymerase II holoenzyme is a form of eukaryotic RNA polymerase II that is recruited to the promoters ...

ESRRB Estrogen-related receptor beta (ERR-β), also known as ESRRB or NR3B2 (nuclear receptor subfamily 3, group B, member 2), is a nuclear receptor that in humans is encoded by the ''ESRRB'' (Estrogen Related Receptor Beta) gene In biology, th ...

References

{{Reflist Epigenetics