title: The interplay of histone modifications - writers that read.
abstract: Histones are subject to a vast array of posttranslational modifications including acetylation, methylation, phosphorylation, and ubiquitylation. The writers of these modifications play important roles in normal development and their mutation or misregulation is linked with both genetic disorders and various cancers. Readers of these marks contain protein domains that allow their recruitment to chromatin. Interestingly, writers often contain domains which can read chromatin marks, allowing the reinforcement of modifications through a positive feedback loop or inhibition of their activity by other modifications. We discuss how such positive reinforcement can result in chromatin states that are robust and can be epigenetically maintained through cell division. We describe the implications of these regulatory systems in relation to modifications including H3K4me3, H3K79me3, and H3K36me3 that are associated with active genes and H3K27me3 and H3K9me3 that have been linked to transcriptional repression. We also review the crosstalk between active and repressive modifications, illustrated by the interplay between the Polycomb and Trithorax histone-modifying proteins, and discuss how this may be important in defining gene expression states during development.
authors.affiliation: Developmental Epigenetics, Department of Biochemistry, University of Oxford, Oxford, UK.
authors.forename: Tianyi
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Developmental Epigenetics, Department of Biochemistry, University of Oxford, Oxford, UK sarah.cooper@bioch.ox.ac.uk.
authors.forename: Sarah
authors.initials: S
authors.lastname: Cooper
authors.affiliation: Developmental Epigenetics, Department of Biochemistry, University of Oxford, Oxford, UK.
authors.forename: Neil
authors.initials: N
authors.lastname: Brockdorff
mesh_terms: D000818:Animals; D002843:Chromatin / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D042421:Histone Code; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008745:Methylation; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics / Q000378:metabolism; D063146:Polycomb-Group Proteins / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; D006657:Histones; C497422:KMT2A protein, human; D063146:Polycomb-Group Proteins; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase
keywords: Polycomb; Trithorax; chromatin; histone modifications