Mitotic Bookmarking
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Bookmarking (also "gene bookmarking" or "mitotic bookmarking") refers to a potential mechanism of transmission of gene expression programs through cell division. During mitosis,
gene transcription Transcription is the process of copying a segment of DNA into RNA. The segments of DNA transcribed into RNA molecules that can encode proteins are said to produce messenger RNA (mRNA). Other segments of DNA are copied into RNA molecules called ...
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 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 roles in 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 mitosis, the promoters of genes that exist in a
transcription Transcription refers to the process of converting sounds (voice, music etc.) into letters or musical notes, or producing a copy of something in another medium, including: Genetics * Transcription (biology), the copying of DNA into RNA, the fir ...
-competent state become "marked" in some way, * this "mark" persists both during and after mitosis, 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 of a single RNA transcript from the DNA downstream of the promoter. The RNA transcript may encode a protein (mRNA), or can have a function in and of ...
s during mitosis. 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. They act as spools around which DNA winds to create structural units called nucleosomes. Nucleosomes in turn a ...
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 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 *
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 by ...
*
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. Intracellularly localized Hsp70s are an import ...
*
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 o ...
* ESRRB


References

{{Reflist Epigenetics