Expression, Purification, and Biophysical Studies of Chromodomain Proteins

Nielsen, Peter R.; Callaghan, Juliana; Murzina, Natalia V.; Laue, Ernest D.

doi:10.1016/s0076-6879(03)76010-8

Cited by 3 publications

(3 citation statements)

References 28 publications

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“…Within the conserved CD, the second and third β-strands can be connected by loops of variable lengths. However, CDs with longer or shorter linkers connecting the β-sheets to the helix are not found throughout evolution, as they would disrupt the core of structure [29]. This is consistent with the results of structural comparisons, which indicate that the CD of this human protein is conserved among isoforms and those present in evolutionarily distant organisms such as yeast, flies, and plants (Table 1).…”

Section: Modeling Shp1γ As a Csd-less Protein With The Ability To Binsupporting

confidence: 84%

“…For instance, the lack of the CSD used for heterodimerization among the conventional HP1α, HP1β, and HP1γ, as well as for recruiting many other partners that regulate many cellular functions, is highly suggestive that sHP1γ will have some divergent functions. If the protein behaves more like other CSD-less CBX members [29], one could expect that it may use the CD for the dual function of binding histones and forming complexes with other proteins. However, the formation of complexes with other HP1-interacting proteins may not be feasible for sHP1γ.…”

Section: Discussionmentioning

confidence: 99%

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Discovery, expression, cellular localization, and molecular properties of a novel, alternative spliced HP1γ isoform, lacking the chromoshadow domain

et al. 2020

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By reading the H3K9Me3 mark through their N-terminal chromodomain (CD), HP1 proteins play a significant role in cancer-associated processes, including cell proliferation, differentiation, chromosomal stability, and DNA repair. Here, we used a combination of bioinformaticsbased methodologies, as well as experimentally-derived datasets, that reveal the existence of a novel short HP1γ (CBX3) isoform, named here sHP1γ, generated by alternative splicing of the CBX3 locus. The sHP1γ mRNA encodes a protein composed of 101 residues and lacks the C-terminal chromoshadow domain (CSD) that is required for dimerization and heterodimerization in the previously described 183 a. a HP1γ protein. Fold recognition, order-to-disorder calculations, threading, homology-based molecular modeling, docking, and molecular dynamic simulations show that the sHP1γ is comprised of a CD flanked by intrinsically disordered regions (IDRs) with an IDR-CD-IDR domain organization and likely retains the ability to bind to the H3K9Me3. Both qPCR analyses and mRNA-seq data derived from large-scale studies confirmed that sHP1γ mRNA is expressed in the majority of human tissues at approximately constant ratios with the chromoshadow domain containing isoform. However, sHP1γ mRNA levels appear to be dysregulated in different cancer types. Thus, our data supports the notion that, due to the existence of functionally different isoforms, the regulation of HP1γ-mediated functions is more complex than previously anticipated.

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Section: Modeling Shp1γ As a Csd-less Protein With The Ability To Binsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Discovery, expression, cellular localization, and molecular properties of a novel, alternative spliced HP1γ isoform, lacking the chromoshadow domain

et al. 2020

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“…For example, the Drosophila Mi-2 chromo domain has been shown to bind DNA (18). However, structure-guided sequence analysis indicates that a significant fraction of proteins, which are widely believed to contain chromo domains because they contain a short "chromo box" sequence motif (2), does not conform to this canonical fold (19,20). Examples of such proteins include members of the Drosophila dosage compensation complex: MSL3 and MOF.…”

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confidence: 99%

Structure of the Chromo Barrel Domain from the MOF Acetyltransferase

Nielsen

Nietlispach

Buscaino

et al. 2005

Journal of Biological Chemistry

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We report here the structure of the putative chromo domain from MOF, a member of the MYST family of histone acetyltransferases that acetylates histone H4 at Lys-16 and is part of the dosage compensation complex in Drosophila. We found that the structure of this domain is a ␤-barrel that is distinct from the ␣ ؉ ␤ fold of the canonical chromo domain. Despite the differences, there are similarities that support an evolutionary relationship between the two domains, and we propose the name "chromo barrel." The chromo barrel domains may be divided into two groups, MSL3-like and MOF-like, on the basis of whether a group of conserved aromatic residues is present or not. The structure suggests that, although the MOF-like domains may have a role in RNA binding, the MSL3-like domains could instead bind methylated residues. The MOF chromo barrel shares a common fold with other chromatin-associated modules, including the MBT-like repeat, Tudor, and PWWP domains. This structural similarity suggests a probable evolutionary pathway from these other modules to the canonical chromo domains (or vice versa) with the chromo barrel domain representing an intermediate structure.

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Phosphorylation of repressive histone code readers by casein kinase 2 plays diverse roles in heterochromatin regulation

Murakami

2019

The Journal of Biochemistry

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Heterochromatin is a condensed and transcriptionally silent chromatin structure and that plays important roles in epigenetic regulation of the genome. Two types of heterochromatin exist: constitutive heterochromatin is primarily associated with trimethylation of histone H3 at lysine 9 (H3K9me3), and facultative heterochromatin with trimethylation of H3 at lysine 27 (H3K27me3). The methylated histones are bound by the chromodomain of histone code ‘reader’ proteins: HP1 family proteins for H3K9me3 and Polycomb family proteins for H3K27me3. Each repressive reader associates with various ‘effector’ proteins that provide the functional basis of heterochromatin. Heterochromatin regulation is primarily achieved by controlling histone modifications. However, recent studies have revealed that the repressive readers are phosphorylated, like other regulatory proteins, suggesting that phosphorylation also participates in heterochromatin regulation. Detailed studies have shown that phosphorylation of readers affects the binding specificities of chromodomains for methylated histone H3, as well as the binding of effector proteins. Thus, phosphorylation adds another layer to heterochromatin regulation. Interestingly, casein kinase 2, a strong and predominant kinase within the cell, is responsible for phosphorylation of repressive readers. In this commentary, I summarize the regulation of repressive readers by casein kinase 2-dependent phosphorylation and discuss the functional meaning of this modification.

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Expression, Purification, and Biophysical Studies of Chromodomain Proteins

Cited by 3 publications

References 28 publications

Discovery, expression, cellular localization, and molecular properties of a novel, alternative spliced HP1γ isoform, lacking the chromoshadow domain

Discovery, expression, cellular localization, and molecular properties of a novel, alternative spliced HP1γ isoform, lacking the chromoshadow domain

Structure of the Chromo Barrel Domain from the MOF Acetyltransferase

Phosphorylation of repressive histone code readers by casein kinase 2 plays diverse roles in heterochromatin regulation

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