title: A Subset of Human Bromodomains Recognizes Butyryllysine and Crotonyllysine Histone Peptide Modifications.
abstract: Bromodomains are epigenetic readers that are recruited to acetyllysine residues in histone tails. Recent studies have identified non-acetyl acyllysine modifications, raising the possibility that these might be read by bromodomains. Profiling the nearly complete human bromodomain family revealed that while most human bromodomains bind only the shorter acetyl and propionyl marks, the bromodomains of BRD9, CECR2, and the second bromodomain of TAF1 also recognize the longer butyryl mark. In addition, the TAF1 second bromodomain is capable of binding crotonyl marks. None of the human bromodomains tested binds succinyl marks. We characterized structurally and biochemically the binding to different acyl groups, identifying bromodomain residues and structural attributes that contribute to specificity. These studies demonstrate a surprising degree of plasticity in some human bromodomains but no single factor controlling specificity across the family. The identification of candidate butyryl- and crotonyllysine readers supports the idea that these marks could have specific physiological functions.
authors.affiliation: Department of Early Discovery Biochemistry, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
authors.forename: E Megan
authors.initials: EM
authors.lastname: Flynn
authors.affiliation: Department of Early Discovery Biochemistry, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
authors.forename: Oscar W
authors.initials: OW
authors.lastname: Huang
authors.affiliation: Department of Structural Biology, Constellation Pharmaceuticals, Inc., 215 First Street, Suite 200, Cambridge, MA 02142, USA.
authors.forename: Florence
authors.initials: F
authors.lastname: Poy
authors.affiliation: Department of Early Discovery Biochemistry, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
authors.forename: Mariano
authors.initials: M
authors.lastname: Oppikofer
authors.affiliation: Department of Structural Biology, Constellation Pharmaceuticals, Inc., 215 First Street, Suite 200, Cambridge, MA 02142, USA.
authors.forename: Steve F
authors.initials: SF
authors.lastname: Bellon
authors.affiliation: Department of Structural Biology, Constellation Pharmaceuticals, Inc., 215 First Street, Suite 200, Cambridge, MA 02142, USA. Electronic address: yongtang@broadinstitute.org.
authors.forename: Yong
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Early Discovery Biochemistry, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA. Electronic address: cochran.andrea@gene.com.
authors.forename: Andrea G
authors.initials: AG
authors.lastname: Cochran
mesh_terms: D000215:Acylation; D001665:Binding Sites; D002087:Butyrates / Q000737:chemistry / Q000378:metabolism; D003437:Crotonates / Q000737:chemistry / Q000378:metabolism; D018360:Crystallography, X-Ray; D044127:Epigenesis, Genetic; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D051548:Histone Acetyltransferases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008239:Lysine / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D040081:Protein Array Analysis; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D035381:TATA-Binding Protein Associated Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D035362:Transcription Factor TFIID / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D014867:Water / Q000737:chemistry / Q000378:metabolism; D000092468:Bromodomain Containing Proteins
chemical_list: D002087:Butyrates; D003437:Crotonates; D051548:Histone Acetyltransferases; D006657:Histones; D008239:Lysine; D011994:Recombinant Proteins; D035381:TATA-Binding Protein Associated Factors; D035362:Transcription Factor TFIID; D014157:Transcription Factors; D014867:Water; C587454:BRD9 protein, human; D000092468:Bromodomain Containing Proteins; C576521:Cecr2 protein, human; C069001:TATA-binding protein associated factor 250 kDa