Role of H1 linker histones in mammalian development and stem cell differentiation

Pan, Chenyi; Fan, Yuhong

doi:10.1016/j.bbagrm.2015.12.002

Cited by 65 publications

(72 citation statements)

References 195 publications

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“…H1 proteins are evolutionarily unrelated to the core histones and are characterized by a central winged helix domain, or globular domain, flanked by unstructured N-and C-termini (Cerf et al 1993;Ramakrishnan et al 1993;Kasinsky et al 2001). Early studies showed that animal H1 proteins bind outside of the NCP (Baldwin et al 1975;Shaw et al 1976) and can protect an additional 20bp of DNA from nuclease In vivo studies of mammalian H1 are complicated by the existence of 11 H1 variants that appear to be partially redundant (Pan and Fan 2015). Deletion of single H1 variants failed to produce significant phenotypes in mice (Fan et al 2001), but mice lacking three H1 variants are inviable (Fan et al 2003) and triple-knockout embryonic stem cells (ESCs) are unable to differentiate (Zhang et al 2012a).…”

Section: Introductionmentioning

confidence: 99%

Histone H1 limits DNA methylation inNeurospora crassa

Seymour

Santos

et al. 2016

Preprint

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Histone H1 variants, known as linker histones, are essential chromatin components in higher eukaryotes, yet compared to the core histones relatively little is known about their in vivo functions. The filamentous fungus Neurospora crassa encodes a single H1 protein that is not essential for viability. To investigate the role of N. crassa H1, we constructed a functional FLAG-tagged H1 fusion protein and performed genomic and molecular analyses. Cell fractionation experiments showed that H1-3XFLAG is a chromatin binding protein. Chromatin-immunoprecipitation combined with sequencing (ChIP-seq) revealed that H1-3XFLAG is globally enriched throughout the genome with a subtle preference for promoters of expressed genes. In mammals, the stoichiometry of H1 impacts nucleosome repeat length. To determine if H1 impacts nucleosome occupancy or nucleosome positioning in N. crassa, we performed micrococcal nuclease digestion in the wild-type and the DhH1 strain followed by sequencing (MNase-seq). Deletion of hH1 did not significantly impact nucleosome positioning or nucleosome occupancy. Analysis of DNA methylation by whole-genome bisulfite sequencing (MethylC-seq) revealed a modest but global increase in DNA methylation in the DhH1 mutant. Together, these data suggest that H1 acts as a nonspecific chromatin binding protein that can limit accessibility of the DNA methylation machinery in N. crassa.

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Section: Introductionmentioning

confidence: 99%

Histone H1 limits DNA methylation inNeurospora crassa

Seymour

Santos

et al. 2016

Preprint

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“…This cluster included sets of histone H1 genes that are transcribed with cell cycle-dependent and independent control, which suggests that the difference in the chromatin organisation of this region between pluripotent states is likely to be driven by additional factors that act outside of the cell cycle. Given that the expression and regulation of individual H1 isoforms varies substantially between cell types and these properties are associated closely with pluripotency, differentiation and development (Pan and Fan, 2016;Turinetto and Giachino, 2015), a focused examination of histone H1 function in these cell types would be an interesting future direction of research. More commonly though, we discovered that sub-networks tended to be larger and to contain a greater number of interactions in primed compared to naïve PSCs.…”

Section: Discussionmentioning

confidence: 99%

Network analysis of promoter interactions reveals the hierarchical differences in genome organisation between human pluripotent states

Chovanec

Collier

Krueger

et al. 2019

Preprint

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SUMMARYA complex and poorly understood interplay between 3D genome organisation, transcription factors and chromatin state underpins cell identity. To gain a systems-level understanding of this interplay, we generated a high-resolution atlas of annotated chromatin interactions in naïve and primed human pluripotent stem cells and developed a network-graph approach to examine the atlas at multiple spatial scales. Investigating chromatin interactions as a network uncovered highly connected hubs that changed substantially in interaction frequency and in transcriptional co-regulation between pluripotent states.Small hubs frequently merged to form larger networks in primed cells, often linked by newly-formed Polycomb-associated interactions. Importantly, we identified state-specific differences in enhancer activity and interactivity that corresponded with widespread reconfiguration of transcription factor binding and target gene expression. These findings provide multilayered insights into the gene regulatory control of human pluripotency and our systems-based network approach could be applied broadly to uncover new principles of 3D genome organisation. RESULTS Promoter interaction mapping in naïve and primed human PSCsWe used PCHi-C to profile the global, high-resolution interactomes of 22,101 promoters in isogenic human naïve and primed PSCs. There was a strong concordance in pairwise interaction read counts between the biological replicates of the same cell type (r 2 >0.95; Figure S1A); therefore we merged replicates for all downstream analyses. PCHi-C data normalisation and signal detection using the CHiCAGO pipeline (Cairns et al., 2016) identified 75,091 significant cis-interactions between baited promoters and other genomic regions in naïve PSCs, and 83,782 in primed PSCs ( Figure S1B). Just under half of the interactions were common to both cell types (n=39,360). As expected, trans-interactions represented a small minority of promoter interactions (354 interactions). In both cell types, the majority of significant interactions were between the promoters of protein-coding genes and non-promoter genomic regions ( Figure S1B).Processed datasets from this large-scale resource are available through the Open Science Framework (https://osf.io/XXXXX) and Table S1, and raw sequencing reads have been deposited to the Gene Expression Omnibus (accession GSEXXXXXX). Network visualisation of promoter interactomesWe next developed a computational approach called Canvas (Chromosome architecture network visualisation at scales) to visualise high-resolution, capture-based DNA interaction data at a network scale.Network graphs were constructed where each node of the network represents an individual HindIII genomic fragment (average size, 4 kb) and each edge represents a significant interaction between nodes ( Figure 1A). We combined all significant interactions detected in naïve and primed PSCs to produce a single, unified network graph, which retains information about whether an interaction is shared or cell type-specific ( Figu...

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“…[6][7][8] Conversely, the cluster H1 members are induced through the major zygotic gene activation, and incorporated into the chromatin. 9 To date, each of the somatic H1 members (H1f0, and H1.1-H1.5) has been investigated only as a percentage of the total histones in midgestation embryos, 10,11 and the individual expression patterns in the subsequent stages of embryogenesis have not been fully defined. H1f0 is rarely expressed during embryogenesis; rather, it is accumulated in the terminally differentiated cells at the postnatal stage.…”

Section: Research-article2017mentioning

confidence: 99%

“…Although the single-knockout mice of each H1 variant are phenotypically normal, 17,18 the triple-knockout mice of H1.2, H1.3, and H1.4 caused the embryonic lethality at E11.5 by a broad spectrum of developmental defects. 11,19 In terms of H1fx protein, there has been no report about its expression pattern during mammalian embryogenesis. H1fx is the most recently identified and thus the least characterized of the H1 family members.…”

Section: Research-article2017mentioning

confidence: 99%

Temporally and Spatially Regulated Expression of the Linker Histone H1fx During Mouse Development

Ichihara-Tanaka

Kadomatsu

Kishida

2017

J Histochem Cytochem.

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The linker histone H1fx is the least characterized member of the H1 family. To investigate the developmental changes of H1fx, we performed an immunohistochemical analysis of its expression pattern from embryos to adult mice. We found that H1fx was highly expressed during gastrulation, and was positive in all embryonic germ layers between E8.5 and E10.5, which mostly overlapped with the expression of the proliferation marker Ki-67. Neural and mesenchyme tissues strongly expressed H1fx at E10.5. H1fx expression began to be restricted at around E12.5. Western blot analysis of brain tissues demonstrated that the total expression level of H1fx gradually decreased with time from E12.5 to adulthood, whereas H1f0 was increased over this period. In adult mice, H1fx was restrictively expressed at the hypothalamus, subventricular zone, subgranular zone, medulla of the adrenal grand, islets of Langerhans, and myenteric plexus. Taken together, these data suggest that H1fx is preferentially expressed in immature embryonic cells and plays some roles in cells with neural properties.

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Role of H1 linker histones in mammalian development and stem cell differentiation

Cited by 65 publications

References 195 publications

Histone H1 limits DNA methylation inNeurospora crassa

Histone H1 limits DNA methylation inNeurospora crassa

Network analysis of promoter interactions reveals the hierarchical differences in genome organisation between human pluripotent states

Temporally and Spatially Regulated Expression of the Linker Histone H1fx During Mouse Development

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