Phosphorylation of Histone H3 Is Required for Proper Chromosome Condensation and Segregation

Yi, Wei; Yu, Lanlan; Bowen, Josephine; Gorovsky, Martin A.; Allis, C. David

doi:10.1016/s0092-8674(00)80718-7

Cited by 648 publications

(548 citation statements)

References 61 publications

Supporting

Mentioning

511

Contrasting

Unclassified

Order By: Relevance

“…Thus, it is possible that the DNA-binding activity of CTCF is regulated by an unknown protein kinase in addition to TOPK/PBK and Cdk1. It has been proposed that mitotic chromosomes exist in a highly condensed state to ensure stable and integral chromosome segregation [21]. Because transcription-related factors are excluded from mitotic chromatin, mitotic chromosomes are transcriptionally inactive [15].…”

Section: Discussionmentioning

confidence: 99%

Mitotic phosphorylation of CCCTC‐binding factor (CTCF) reduces its DNA binding activity

et al. 2017

View full text Add to dashboard Cite

During mitosis, higher order chromatin structures are disrupted and chromosomes are condensed to achieve accurate chromosome segregation. CCCTC‐binding factor (CTCF) is a highly conserved and ubiquitously expressed C2H2‐type zinc finger protein which is considered to be involved in epigenetic memory through regulation of higher order chromatin architecture. However, the regulatory mechanism of CTCF in mitosis is still unclear. Here we found that the DNA‐binding activity of CTCF is regulated in a phosphorylation‐dependent manner during mitosis. The linker domains of the CTCF zinc finger domain were found to be phosphorylated during mitosis. The phosphorylation of linker domains impaired the DNA‐binding activity in vitro. Mutation analyses showed that amino acid residues (Thr289, Thr317, Thr346, Thr374, Ser402, Ser461, and Thr518) located in the linker domains were phosphorylated during mitosis. Based on these results, we propose that the mitotic phosphorylation of the linker domains of CTCF is important for the dissociation of CTCF from mitotic chromatin.

show abstract

Section: Discussionmentioning

confidence: 99%

Mitotic phosphorylation of CCCTC‐binding factor (CTCF) reduces its DNA binding activity

et al. 2017

View full text Add to dashboard Cite

show abstract

“…These three kinases control most mitotic events, including centrosome maturation and separation, chromosome orientation and segregation [8]. Notably, histone H3 is a substrate for the Aurora kinases and is phosphorylated at serine 10 only during the length of M phase [108,109]. Phosphohistone H3 (H3S10ph) is therefore an M phase marker.…”

Section: Geminin Mitotic Kinases and Phosphohistone H3 Can Be Used Tmentioning

confidence: 99%

The cell cycle and cancer

Williams

Stoeber

2011

The Journal of Pathology

543

406

View full text Add to dashboard Cite

Deregulation of the cell cycle underlies the aberrant cell proliferation that characterizes cancer and loss of cell cycle checkpoint control promotes genetic instability. During the past two decades, cancer genetics has shown that hyperactivating mutations in growth signalling networks, coupled to loss of function of tumour suppressor proteins, drives oncogenic proliferation. Gene expression profiling of these complex and redundant mitogenic pathways to identify prognostic and predictive signatures and their therapeutic targeting has, however, proved challenging. The cell cycle machinery, which acts as an integration point for information transduced through upstream signalling networks, represents an alternative target for diagnostic and therapeutic interventions. Analysis of the DNA replication initiation machinery and mitotic engine proteins in human tissues is now leading to the identification of novel biomarkers for cancer detection and prognostication, and is providing target validation for cell cycle-directed therapies.

show abstract

“…12 Histone H3 phosphorylation at Ser 10 is closely related to induction of immediate-early (IE) genes, chromatin remodeling and chromatin condensation during mitosis and meiosis. 13 Ser 10 phosphorylation of histone H3 is also correlated with the transcriptional activation of mitogeninduced genes. 14 Ser 28 phosphorylation of histone H3 also appears in response to stimulation of the mitogen-activated protein kinase (MAPK) pathways involving activation of extracellular signal-regulated kinases and p38 MAPK at a time when IE genes are expressed.…”

mentioning

confidence: 99%

Tumor suppressor pp32 represses cell growth through inhibition of transcription by blocking acetylation and phosphorylation of histone H3 and initiating its proapoptotic activity

Fan

Zhang

2005

Cell Death Differ

View full text Add to dashboard Cite

pp32 belongs to a family of leucine-rich acidic nuclear proteins, which play important roles in many cellular processes including regulation of chromatin remodeling, transcription, RNA transport, transformation and apoptosis. pp32 is described as a new tumor suppressor. It is unknown as to how pp32 works in tumor suppression. We found that overexpression of pp32 in human Jurkat T cells inhibits cell growth, and silenced pp32 promotes growth. We first showed that hyperacetylation and hyperphosphorylation of histone H3 are required for T-cell activation. Phosphorylation of histone H3 precedes acetylation during T-cell activation. pp32 specifically binds to histone H3 and blocks its acetylation and phosphorylation. pp32 directly initiates caspase activity and also promotes granzyme A-mediated caspase-independent cell death. Taken together, pp32 plays a repressive role by inhibiting transcription and triggering apoptosis.

show abstract

Phosphorylation of Histone H3 Is Required for Proper Chromosome Condensation and Segregation

Cited by 648 publications

References 61 publications

Mitotic phosphorylation of CCCTC‐binding factor (CTCF) reduces its DNA binding activity

Mitotic phosphorylation of CCCTC‐binding factor (CTCF) reduces its DNA binding activity

The cell cycle and cancer

Tumor suppressor pp32 represses cell growth through inhibition of transcription by blocking acetylation and phosphorylation of histone H3 and initiating its proapoptotic activity

Contact Info

Product

Resources

About