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 is silenced and most
transcription factors 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
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 ...
, the
promoters of genes that exist in a
transcription-competent state become "marked" in some way,
* this "mark" persists both during and after
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 ...
, 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 promoters 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 ...
. 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 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
*
HSP70
*
TFIID
*
ESRRB
References
{{Reflist
Epigenetics