title: Bivalent Histone Modifications and Development.
abstract: BACKGROUND
  Development is an epigenetic regulation dependent event. As one pretranscriptional regulator, bivalent histone modifications were observed to be involved in development recently. It is believed that histone methylation potentially takes charge of cell fate determination and differentiation. The synchronous existence of functionally opposite histone marks at transcript start sequence (TSS) is defined as "Bivalency", which mainly mark development related genes. H3K4me3 and H3K27me3, the prominent histone methylations of bivalency, are implicated in transcriptional activation and transcriptional repression respectively. The delicate balance between H3K4me3 and H3K27me3 produces diverse chromatin architectures, resulting in different transcription states of downstream genes: "poised", "activated" or "repressed".
  
  
  OBJECTIVE
  In order to explore the developmental role of bivalent histone modification and the underlying mechanism, we did systematic review and rigorous assessment about relative literatures.
  
  
  RESULTS
  Bivalent histone modifications are considered to set up genes for activation during lineage commitment by H3K4me3 and repress lineage control genes to maintain pluripotency by H3K27me3. Summarily, bivalency in stem cells keeps stemness via poising differentiation relevant genes. After receiving developmental signals, the balance between "gene activation" and "gene repression" is broken, which turns genes transcription state from "poised" effect to switch on or switch off effect, thus initiates irreversible and spontaneous differentiation procedures.
  
  
  CONCLUSIONS
  Bivalent histone modifications and the associated histone-modifying complexes safeguard proper and robust differentiation of stem cells, thus playing an essential role in development.
authors.affiliation: State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.|West China School of Stomatology, Sichuan University, Chengdu, China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Li
authors.affiliation: State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.|West China School of Stomatology, Sichuan University, Chengdu, China.
authors.forename: Mian
authors.initials: M
authors.lastname: Wan
authors.affiliation: State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.|West China School of Stomatology, Sichuan University, Chengdu, China.
authors.forename: Binpeng
authors.initials: B
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.|West China School of Stomatology, Sichuan University, Chengdu, China.
authors.forename: Yiran
authors.initials: Y
authors.lastname: Peng
authors.affiliation: State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.|West China School of Stomatology, Sichuan University, Chengdu, China.
authors.forename: Yachuan
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.|West China School of Stomatology, Sichuan University, Chengdu, China.
authors.forename: Caixia
authors.initials: C
authors.lastname: Pi
authors.affiliation: State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.|West China School of Stomatology, Sichuan University, Chengdu, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.|West China School of Stomatology, Sichuan University, Chengdu, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Ye
authors.affiliation: State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.|West China School of Stomatology, Sichuan University, Chengdu, China.
authors.forename: Xuedong
authors.initials: X
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.|West China School of Stomatology, Sichuan University, Chengdu, China.
authors.forename: Liwei
authors.initials: L
authors.lastname: Zheng
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D002843:Chromatin / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000166:cytology; D044127:Epigenesis, Genetic / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D006657:Histones / Q000378:metabolism*; D006801:Humans
chemical_list: D002843:Chromatin; D006657:Histones
keywords: ESCs differentiation; H3K27me3; H3K4me3; bivalent mark; development; organogenesis