title: How chromatin-binding modules interpret histone modifications: lessons from professional pocket pickers.
abstract: Histones comprise the major protein component of chromatin, the scaffold in which the eukaryotic genome is packaged, and are subject to many types of post-translational modifications (PTMs), especially on their flexible tails. These modifications may constitute a 'histone code' and could be used to manage epigenetic information that helps extend the genetic message beyond DNA sequences. This proposed code, read in part by histone PTM-binding 'effector' modules and their associated complexes, is predicted to define unique functional states of chromatin and/or regulate various chromatin-templated processes. A wealth of structural and functional data show how chromatin effector modules target their cognate covalent histone modifications. Here we summarize key features in molecular recognition of histone PTMs by a diverse family of 'reader pockets', highlighting specific readout mechanisms for individual marks, common themes and insights into the downstream functional consequences of the interactions. Changes in these interactions may have far-reaching implications for human biology and disease, notably cancer.
authors.affiliation: Laboratory of Chromatin Biology, The Rockefeller University, New York, New York 10021, USA.
authors.forename: Sean D
authors.initials: SD
authors.lastname: Taverna
authors.affiliation: Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
authors.forename: Haitao
authors.initials: H
authors.lastname: Li
authors.affiliation: Laboratory of Chromatin Biology, The Rockefeller University, New York, New York 10021, USA.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Ruthenburg
authors.affiliation: Laboratory of Chromatin Biology, The Rockefeller University, New York, New York 10021, USA.
authors.forename: C David
authors.initials: CD
authors.lastname: Allis
authors.affiliation: Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
authors.forename: Dinshaw J
authors.initials: DJ
authors.lastname: Patel
mesh_terms: D048948:14-3-3 Proteins / Q000737:chemistry / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing; D000596:Amino Acids / Q000737:chemistry / Q000378:metabolism; D018797:Cell Cycle Proteins; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D044127:Epigenesis, Genetic; D051548:Histone Acetyltransferases; D006657:Histones / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D035381:TATA-Binding Protein Associated Factors / Q000737:chemistry / Q000378:metabolism; D015534:Trans-Activators / Q000737:chemistry / Q000378:metabolism; D035362:Transcription Factor TFIID / Q000737:chemistry / Q000378:metabolism; D050880:p300-CBP Transcription Factors / Q000737:chemistry / Q000378:metabolism; D000099224:p300-CBP-Associated Factor
chemical_list: D048948:14-3-3 Proteins; D048868:Adaptor Proteins, Signal Transducing; D000596:Amino Acids; D018797:Cell Cycle Proteins; D002843:Chromatin; D004268:DNA-Binding Proteins; D051548:Histone Acetyltransferases; D006657:Histones; D009687:Nuclear Proteins; D035381:TATA-Binding Protein Associated Factors; D015534:Trans-Activators; D035362:Transcription Factor TFIID; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C468783:H2AX protein, human; C413163:MDC1 protein, human; C069001:TATA-binding protein associated factor 250 kDa