Identification and characterization of small molecules that inhibit binding of the third plant homeodomain finger of JARID1A to histone H3

Nucleosomal incorporation of specialized histone variants is an important mechanism to generate different functional chromatin states. Here, we describe the identification and characterization of two novel primate-specific histone H3 variants, H3.X and H3.Y. Their messenger RNAs are found in certain human cell lines, in addition to several normal and malignant human tissues. In keeping with their primate specificity, H3.X and H3.Y are detected in different brain regions. Transgenic H3.X and H3.Y proteins are stably incorporated into chromatin in a similar fashion to the known H3 variants. Importantly, we demonstrate biochemically and by mass spectrometry that endogenous H3.Y protein exists in vivo, and that stress stimuli, such as starvation and cellular density, increase the abundance of H3.Y-expressing cells. Global transcriptome analysis revealed that knockdown of H3.Y affects cell growth and leads to changes in the expression of many genes involved in cell cycle control. Thus, H3.Y is a novel histone variant involved in the regulation of cellular responses to outside stimuli.

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Identification and characterization of Smyd2: a split SET/MYND domain-containing histone H3 lysine 36-specific methyltransferase that interacts with the Sin3 histone deacetylase complex

Molecular Cancer ◽

10.1186/1476-4598-5-26 ◽

2006 ◽

Vol 5 (1) ◽

Cited By ~ 177

Author(s):

Mark A Brown ◽

Robert J Sims ◽

Paul D Gottlieb ◽

Philip W Tucker

Keyword(s):

Histone Deacetylase ◽

Histone H3 ◽

Identification And Characterization

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The Yng1p Plant Homeodomain Finger Is a Methyl-Histone Binding Module That Recognizes Lysine 4-Methylated Histone H3

Molecular and Cellular Biology ◽

10.1128/mcb.00573-06 ◽

2006 ◽

Vol 26 (21) ◽

pp. 7871-7879 ◽

Cited By ~ 114

Author(s):

David G. E. Martin ◽

Kristin Baetz ◽

Xiaobing Shi ◽

Kay L. Walter ◽

Vicki E. MacDonald ◽

...

Keyword(s):

Histone H3 ◽

General Role ◽

Histone Binding ◽

Phd Finger ◽

Amino Terminal ◽

Plant Homeodomain Finger ◽

Plant Homeodomain ◽

Insight Into

ABSTRACT The ING (inhibitor of growth) protein family includes a group of homologous nuclear proteins that share a highly conserved plant homeodomain (PHD) finger domain at their carboxyl termini. Members of this family are found in multiprotein complexes that posttranslationally modify histones, suggesting that these proteins serve a general role in permitting various enzymatic activities to interact with nucleosomes. There are three members of the ING family in Saccharomyces cerevisiae: Yng1p, Yng2p, and Pho23p. Yng1p is a component of the NuA3 histone acetyltransferase complex and is required for the interaction of NuA3 with chromatin. To gain insight into the function of the ING proteins, we made use of a genetic strategy to identify genes required for the binding of Yng1p to histones. Using the toxicity of YNG1 overexpression as a tool, we showed that Yng1p interacts with the amino-terminal tail of histone H3 and that this interaction can be disrupted by loss of lysine 4 methylation within this tail. Additionally, we mapped the region of Yng1p required for overexpression of toxicity to the PHD finger, showed that this region capable of binding lysine 4-methylated histone H3 in vitro, and demonstrated that mutations of the PHD finger that abolish binding in vitro are no longer toxic in vivo. These results identify a novel function for the Yng1p PHD finger in promoting stabilization of the NuA3 complex at chromatin through recognition of histone H3 lysine 4 methylation.

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Seismic identification and characterization of the third Bed of the Member 4 of Leikoupo Formation of Middle Triassic in Southwest Sichuan Basin

10.1190/carbonate2017-20 ◽

2017 ◽

Author(s):

Changlong He ◽

Tianjun Huang ◽

Yan Lv ◽

Wenzheng Lv

Keyword(s):

Sichuan Basin ◽

Middle Triassic ◽

The Third ◽

Leikoupo Formation ◽

Identification And Characterization

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Binding and allosteric transmission of histone H3 Lys-4 trimethylation to the recombinase RAG-1 are separable functions of the RAG-2 plant homeodomain finger

Journal of Biological Chemistry ◽

10.1074/jbc.ra120.014382 ◽

2020 ◽

Vol 295 (27) ◽

pp. 9052-9060

Author(s):

Meiling R. May ◽

John T. Bettridge ◽

Stephen Desiderio

Keyword(s):

Gene Transcription ◽

Conformational Changes ◽

Histone H3 ◽

Active Chromatin ◽

Phd Finger ◽

Separable Functions ◽

Plant Homeodomain Finger ◽

Plant Homeodomain ◽

Recombination Activating Gene ◽

Rag 1

V(D)J recombination is initiated by the recombination-activating gene protein (RAG) recombinase, consisting of RAG-1 and RAG-2 subunits. The susceptibility of gene segments to cleavage by RAG is associated with gene transcription and with epigenetic marks characteristic of active chromatin, including histone H3 trimethylated at lysine 4 (H3K4me3). Binding of H3K4me3 by a plant homeodomain (PHD) in RAG-2 induces conformational changes in RAG-1, allosterically stimulating substrate binding and catalysis. To better understand the path of allostery from the RAG-2 PHD finger to RAG-1, here we employed phylogenetic substitution. We observed that a chimeric RAG-2 protein in which the mouse PHD finger is replaced by the corresponding domain from the shark Chiloscyllium punctatum binds H3K4me3 but fails to transmit an allosteric signal, indicating that binding of H3K4me3 by RAG-2 is insufficient to support recombination. By substituting residues in the C. punctatum PHD with the corresponding residues in the mouse PHD and testing for rescue of allostery, we demonstrate that H3K4me3 binding and transmission of an allosteric signal to RAG-1 are separable functions of the RAG-2 PHD finger.

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