Epigenetic virtues of chromodomains

Blus, Bartlomiej J.; Wiggins, Kimberly; Khorasanizadeh, Sepideh

doi:10.3109/10409238.2011.619164

Cited by 59 publications

(61 citation statements)

References 227 publications

(264 reference statements)

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“…S1 and S3). Typically, methyllysine binding aromatic cages, such as those found in chromo and other tudor domains, are formed by three aromatic residues (3,14). An interesting case is the PHD finger of BPTF, which also uses an aromatic cage of four residues to bind H3K4me3 (15).…”

Section: Resultsmentioning

confidence: 99%

Distinct mode of methylated lysine-4 of histone H3 recognition by tandem tudor-like domains of Spindlin1

Yang

Wang

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Recognition of methylated histone tail lysine residues by tudor domains plays important roles in epigenetic control of gene expression and DNA damage response. Previous studies revealed the binding of methyllysine in a cage of aromatic residues, but the molecular mechanism by which the sequence specificity for surrounding histone tail residues is achieved remains poorly understood. In the crystal structure of a trimethylated histone H3 lysine 4 (H3K4) peptide bound to the tudor-like domains of Spindlin1 presented here, an atypical mode of methyllysine recognition by an aromatic pocket of Spindlin1 is observed. Furthermore, the histone sequence is recognized in a distinct manner involving the amino terminus and a pair of arginine residues of histone H3, and disruption of the binding impaired stimulation of pre-RNA expression by Spindlin1. Our analysis demonstrates considerable diversities of methyllysine recognition and sequence-specific binding of histone tails by tudor domains, and the revelation furthers the understanding of tudor domain proteins in deciphering epigenetic marks on histone tails.H istone lysine methylation imparts epigenetic information in chromatin biology, and the transduction of epigenetic signal is mediated by a diverse group of proteins containing methyllysine recognition domains (1). Some of the best known methyllysine recognition modules include chromo, tudor, MBT (Malignant Brain Tumor), and PHD (Plant Homeodomain) domains (2-4). A recent addition of this family of histone methyllysine "readers" is the BAH domain ORC1 (5). These methyllysine "readers" can recognize histone lysine methylation in a site-specific and methylation state-specific manner. A common feature of methyllysine recognitions involves a cage of aromatic residues, whereas the ways for discriminating the surrounding amino acid sequence of histones appear to be divergent among different methyllysine "readers." In this study, we focus on the recognition of trimethylated lysine-4 of histone H3 (H3K4me3) by the tandem tudor-like domains of Spindlin1.Mammalian Spindlin1 is a nucleolar protein that localizes to the active ribosomal DNA (rDNA) repeats locus, where it is normally enriched with histone H3K4 and H3K36 methylations, and facilitates rRNA expression (6, 7). Spindlin1 contains three tandem tudor-like domains (8), and we previously demonstrated that the tudor-like domains bind to H3K4me3 in vitro (7). Furthermore, Spindlin1 mutants with impaired H3K4me3 binding showed reduced stimulation of rRNA expression (7). Hence, these observations directly link the ability of H3K4me3 binding with the transcription function of Spindlin1. However, several important aspects of the molecular mechanism of H3K4me3 recognition by Spindlin1 remain outstanding; foremost ones include how Spindlin1 achieves its H3K4me3 specificity and what features distinguish the H3K4me3-binding tudor-like domain from others in Spindlin1. Previous structural studies of tudor domains have yielded some understandings of how they recognize methylated histone ...

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Section: Resultsmentioning

confidence: 99%

Distinct mode of methylated lysine-4 of histone H3 recognition by tandem tudor-like domains of Spindlin1

Yang

Wang

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…H3K9me3 recruits chromodomain-containing proteins, such as HP1, to condense chromatin and silence gene expression. 27 As H3K9me3 recruitment is negatively regulated, in part, through phosphorylation of neighboring serine 10 (H3S10ph), this finding has given rise to the concept of a 'phospho-methyl' switch. 28,29 A similar switch has been shown to eject the H3K4me3-interacting PHD fingers when neighboring H3T3 or H3T6 are phosphorylated.…”

Section: Effect Of Other Neighboring Ptms On the Ability Of Taf14 To mentioning

confidence: 99%

The essential role of acetyllysine binding by the YEATS domain in transcriptional regulation

et al. 2016

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The YEATS domains of AF9 and Taf14 have recently been found to recognize the histone H3K9ac modification. In this commentary, we discuss the mechanistic and biological implications of this interaction. We compare structures of the YEATS-H3K9ac complexes, highlighting a novel mechanism for the acetyllysine recognition through the aromatic cage. We also summarize the latest findings underscoring a critical role of the acetyllysine binding function of AF9 and Taf14 in transcriptional regulation and DNA repair.

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“…PRC1 acts to control gene expression during cellfate specification and differentiation through chromatin modifications, although it is unclear whether the underlying mechanism involves repression of transcriptional machinery or regulation of chromatin structure [Simon and Kingston, 2009]. CBX proteins are thought to mediate the recognition of methylated histones by PRC1 via their conserved chromodomains, though other molecular interactions and roles are reported [Blus et al, 2011]. Embryos lacking Cbx2 have previously been reported to exhibit XY gonadal sex reversal, thereby providing a link between PcG-mediated control of gene expression and testis determination [Katoh-Fukui et al, 1998].…”

Section: Cbx2: a Link Between Epigenetics And Sexmentioning

confidence: 99%

Characterising Novel Pathways in Testis Determination Using Mouse Genetics

Carré

Greenfield²

2014

Sex Dev

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Mammalian sex determination is the process by which the bipotential embryonic genital ridge commits to either the testicular or ovarian fate. The existence of a gonad primordium with 2 possible developmental outcomes, depending on the presence or absence of the Y chromosome, remains a fascinating paradigm for examining the manner in which genes cooperate to establish cell fate and regulate differentiation. Development of the mouse gonad offers a unique model for the investigation of sex determination, characterised by powerful transgenic, genomic and other experimental resources for the study of the molecular control of organogenesis. This review focuses on recent progress in our understanding of mouse testis determination, with an emphasis on multi-locus studies of mutant alleles aimed at constructing pathways of interacting gene products. Studies in 2 broad areas have been especially revealing: (i) identification of pathways required for the appropriate expression of Sry, and (ii) characterisation of the antagonistic interactions between the core testis- (SRY-SOX9-FGF9) and ovary- (RSPO1-WNT4-CTNNB1-FOXL2) determining gene regulatory networks. We discuss these advances with an eye on emerging themes in mammalian sex determination.

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Epigenetic virtues of chromodomains

Cited by 59 publications

References 227 publications

Distinct mode of methylated lysine-4 of histone H3 recognition by tandem tudor-like domains of Spindlin1

Distinct mode of methylated lysine-4 of histone H3 recognition by tandem tudor-like domains of Spindlin1

The essential role of acetyllysine binding by the YEATS domain in transcriptional regulation

Characterising Novel Pathways in Testis Determination Using Mouse Genetics

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