Variants of core histones and their roles in cell fate decisions, development and cancer

  title={Variants of core histones and their roles in cell fate decisions, development and cancer},
  author={Marcus Buschbeck and Sandra B Hake},
  journal={Nature Reviews Molecular Cell Biology},
Histone variants endow chromatin with unique properties and show a specific genomic distribution that is regulated by specific deposition and removal machineries. These variants — in particular, H2A.Z, macroH2A and H3.3 — have important roles in early embryonic development, and they regulate the lineage commitment of stem cells, as well as the converse process of somatic cell reprogramming to pluripotency. Recent progress has also shed light on how mutations, transcriptional deregulation and… 
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It is proposed that differences in deposition of H3 variants are largely dependent on the phase of the cell cycle and cellular potency but are also affected by cellular stress and changes in cell fate.
Histone Variants: Guardians of Genome Integrity
Current knowledge on how alterations in histone variant sequence, expression, and deposition into chromatin fuel oncogenic transformation by impacting cell proliferation and cell fate transitions is presented and recent advances in deciphering are reviewed.
Solid tumours hijack the histone variant network.
Hijacking histone variants and histone chaperones as tumour-promoting or tumours-suppressive players in the pathogenesis of cancer is discussed.
Histone MacroH2A1: A Chromatin Point of Intersection between Fasting, Senescence and Cellular Regeneration
Current molecular evidence based on next generation sequencing data, cell assays and in vivo models supporting different mechanisms that could mediate the function of macroH2A1 in health span and life span are reviewed.
The Histone H3 Family and Its Deposition Pathways.
This chapter introduces the organization of the genome in chromatin with a focus on the basic unit, the nucleosome, which contains histones as the major protein component and reviews current knowledge on the histone H3 family and its variants.
Chromatin regulation and dynamics in stem cells.
Dynamic Activity of Histone H3-Specific Chaperone Complexes in Oncogenesis
This review focuses on the chaperone proteins of H 3.1 and H3.3, including structure, regulation, as well as their oncogenic and tumor suppressive functions in tumorigenesis.


Histone H3 variants and their chaperones during development and disease: contributing to epigenetic control.
The importance of H3 variants in the context of nuclear reprogramming and cell differentiation is integrated, and a case in which the identity of a given genomic locus is propagated across different cell types is described.
Histone variants: nuclear function and disease.
Histone variants in pluripotency and disease
Recent studies that have implicated histone variants in maintaining pluripotency and as causal factors in cancer and other diseases are reviewed.
Dynamics of histone variant H3.3 and its coregulation with H2A.Z at enhancers and promoters
The role of histone variant H3.3 and its coregulation with H2A.Z in chromatin dynamics at enhancers and promoters and transcriptional regulation is focused on.
MacroH2A in stem cells: a story beyond gene repression.
The role of macroH2A in the establishment and maintenance of differentiated states is highlighted and its still poorly recognized function in transcriptional activation is discussed.
Splicing switch of an epigenetic regulator by RNA helicases promotes tumor-cell invasiveness
It is shown that macroH2A1 splicing isoforms differentially regulate the transcription of a set of genes involved in redox metabolism, and reveals a new regulatory pathway in which splicing factors control the expression of histone variant isoforms that in turn drive a transcription program to switch tumor cells to an invasive phenotype.
The histone variant macroH2A is an epigenetic regulator of key developmental genes
Microarray-based analysis in human male pluripotent cells uncovered occupancy of both macroH2A variants at many genes encoding key regulators of development and cell fate decisions, demonstrating an important epigenetic mark involved in the concerted regulation of gene expression programs during cellular differentiation and vertebrate development.
Epigenetic dynamics of stem cells and cell lineage commitment: digging Waddington's canal
The intersection of major epigenetic reprogramming and programming events in the early embryo creates plasticity followed by commitment to the principal cell lineages of the early conceptus.
The histone variant macroH2A suppresses melanoma progression through regulation of CDK8
It is demonstrated that mH2A is a critical component of chromatin that suppresses the development of malignant melanoma, a highly intractable cutaneous neoplasm.