The linker histone Hho1 modulates the activity of ATP-dependent chromatin remodeling complexes

Amigo, Roberto; Farkas, Carlos; Gidi, Cristian; Hepp, Matías I.; Cartes, Natalia; Tarifeno, Estefania; Workman, Jerry L.; Gutiérrez, José L.

doi:10.1016/j.bbagrm.2021.194781

Cited by 6 publications

(2 citation statements)

References 49 publications

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“…The linker histone H1, however, is not well conserved across species, with only 37% of shared sequence identity between humans and budding yeast, while fission yeast lacks a linker histone altogether. S. cerevisiae chromatin is also organized by the high mobility group box family protein Hmo1 which performs similar but not fully overlapping roles to histone H1 [14]. While budding and fission yeasts can serve as excellent models for the core histones due to their high level of conservation with mammalian histone proteins, this is not true of histone H1, so we do not focus on the linker histone in this review.…”

Section: Histones and Nucleosomes In Humans And Yeastmentioning

confidence: 99%

Exploring the Molecular Underpinnings of Cancer-Causing Oncohistone Mutants Using Yeast as a Model

Zhang,

Fawwal,

Spangle

et al. 2023

JoF

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Understanding the molecular basis of cancer initiation and progression is critical in developing effective treatment strategies. Recently, mutations in genes encoding histone proteins that drive oncogenesis have been identified, converting these essential proteins into “oncohistones”. Understanding how oncohistone mutants, which are commonly single missense mutations, subvert the normal function of histones to drive oncogenesis requires defining the functional consequences of such changes. Histones genes are present in multiple copies in the human genome with 15 genes encoding histone H3 isoforms, the histone for which the majority of oncohistone variants have been analyzed thus far. With so many wildtype histone proteins being expressed simultaneously within the oncohistone, it can be difficult to decipher the precise mechanistic consequences of the mutant protein. In contrast to humans, budding and fission yeast contain only two or three histone H3 genes, respectively. Furthermore, yeast histones share ~90% sequence identity with human H3 protein. Its genetic simplicity and evolutionary conservation make yeast an excellent model for characterizing oncohistones. The power of genetic approaches can also be exploited in yeast models to define cellular signaling pathways that could serve as actionable therapeutic targets. In this review, we focus on the value of yeast models to serve as a discovery tool that can provide mechanistic insights and inform subsequent translational studies in humans.

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Section: Histones and Nucleosomes In Humans And Yeastmentioning

confidence: 99%

Exploring the Molecular Underpinnings of Cancer-Causing Oncohistone Mutants Using Yeast as a Model

Zhang,

Fawwal,

Spangle

et al. 2023

JoF

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show abstract

“…Although the metazoan linker histone H1 has been extensively studied, many details of H1 in eukaryotic microorganisms remain unclear. The question of who functions as linker histone H1 in Saccharomyces cerevisiae has long been debated ( 21 - 24 ). Due to the highly homologous amino acid sequence to the globular domain of metazoan H1, Hho1 was characterized as histone H1 in budding yeast ( 25 , 26 ).…”

Section: Introductionmentioning

confidence: 99%

Single-molecule study reveals Hmo1, not Hho1, promotes chromatin assembly in budding yeast

Wang

et al. 2023

mBio

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Linker histone H1 plays a crucial role in various biological processes, including nucleosome stabilization, high-order chromatin structure organization, gene expression, and epigenetic regulation in eukaryotic cells. Unlike higher eukaryotes, little about the linker histone in Saccharomyces cerevisiae is known. Hho1 and Hmo1 are two long-standing controversial histone H1 candidates in budding yeast. In this study, we directly observed at the single-molecule level that Hmo1, but not Hho1, is involved in chromatin assembly in the yeast nucleoplasmic extracts (YNPE), which can replicate the physiological condition of the yeast nucleus. The presence of Hmo1 facilitates the assembly of nucleosomes on DNA in YNPE, as revealed by single-molecule force spectroscopy. Further single-molecule analysis showed that the lysine-rich C -terminal domain (CTD) of Hmo1 is essential for the function of chromatin compaction, while the second globular domain at the C -terminus of Hho1 impairs its ability. In addition, Hmo1, but not Hho1, forms condensates with double-stranded DNA via reversible phase separation. The phosphorylation fluctuation of Hmo1 coincides with metazoan H1 during the cell cycle. Our data suggest that Hmo1, but not Hho1, possesses some functionality similar to that of linker histone in Saccharomyces cerevisiae , even though some properties of Hmo1 differ from those of a canonical linker histone H1. Our study provides clues for the linker histone H1 in budding yeast and provides insights into the evolution and diversity of histone H1 across eukaryotes. IMPORTANCE There has been a long-standing debate regarding the identity of linker histone H1 in budding yeast. To address this issue, we utilized YNPE, which accurately replicate the physiological conditions in yeast nuclei, in combination with total internal reflection fluorescence microscopy and magnetic tweezers. Our findings demonstrated that Hmo1, rather than Hho1, is responsible for chromatin assembly in budding yeast. Additionally, we found that Hmo1 shares certain characteristics with histone H1, including phase separation and phosphorylation fluctuations throughout the cell cycle. Furthermore, we discovered that the lysine-rich domain of Hho1 is buried by its second globular domain at the C -terminus, resulting in the loss of function that is similar to histone H1. Our study provides compelling evidence to suggest that Hmo1 shares linker histone H1 function in budding yeast and contributes to our understanding of the evolution of linker histone H1 across eukaryotes.

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Poly(dA:dT) tracts differentially modulate nucleosome remodeling activity of RSC and ISW1a complexes, exerting tract orientation-dependent and -independent effects

Amigo,

Raiqueo,

Tarifeño

et al. 2023

Preprint

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The establishment and maintenance of nucleosome-free regions (NFRs) are prominent processes within chromatin dynamics. Transcription factors, ATP-dependent chromatin remodeling complexes (CRCs) and DNA sequences are the main factors involved. InSaccharomyces cerevisiae, CRCs such as RSC contribute to chromatin opening at NFRs, while other complexes, including ISW1a, contribute to NFR shrinking. Regarding DNA sequences, growing evidence point to poly(dA:dT) tracts as playing a direct role in the active processes involved in nucleosome positioning dynamics. Intriguingly, poly(dA:dT) tract-containing NFRs span asymmetrically relative to the location of the tract, by a currently unknown mechanism. In order to get insight into the role of poly(dA:dT) tracts in nucleosome remodeling, we performed a systematic analysis of their influence on the activity of ISW1a and RSC complexes, with focus on their effect when located on linker DNA. Our findings revealed that poly(dA:dT) tracts differentially affect the activity of these CRCs. Moreover, we found differences between the effects exerted by the two alternative tract orientations. Our results support a model for the asymmetric chromatin opening that take place around these sequences.

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The linker histone Hho1 modulates the activity of ATP-dependent chromatin remodeling complexes

Cited by 6 publications

References 49 publications

Exploring the Molecular Underpinnings of Cancer-Causing Oncohistone Mutants Using Yeast as a Model

Exploring the Molecular Underpinnings of Cancer-Causing Oncohistone Mutants Using Yeast as a Model

Single-molecule study reveals Hmo1, not Hho1, promotes chromatin assembly in budding yeast

Poly(dA:dT) tracts differentially modulate nucleosome remodeling activity of RSC and ISW1a complexes, exerting tract orientation-dependent and -independent effects

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