Similar Datasets
Project description:H1 linker histones are the most abundant chromatin binding proteins. Their association with chromatin determines the spacing between nucleosomes and enables arrays of nucleosomes to fold into more compact chromatin structures. Mammals express multiple H1 proteins and are able to compensate for the loss of one or even two members by increasing synthesis of other members to maintain a constant H1 to nucleosome stoichiometry. To study the role of H1 in mammalian development, we generated a conditional triple H1 knockout (H1cTKO) mouse strain that enables depletion of H1 in specific cell types. Here, we report on the effects of depleting H1 in adult hematopoietic cells. Deletion of the genes encoding three widely expressed H1 subtypes (H1c, H1d, and H1e) has particularly profound effects on B- and T- lymphocyte development. H1 depletion leads to de-repression of T-cell activation genes, and a shift in T-cells towards effector functions, a process that mimics normal T-cell activation. Comparison of chromatin structure in normal and H1-depleted CD8+ T-cells revealed that H1 binding produces localized chromatin compaction within spatially defined chromatin domains containing above average levels of H1. Reduction of H1 stoichiometry in these regions leads to decreases in H3K27 methylation and increases in H3K36 methylation. In vitro, H1 promotes PRC2-mediated H3K27 methylation and inhibits NSD2-mediated H3K36 methylation. Mechanistically, H1 mediates these opposite effects by promoting physical compaction of the chromatin substrate. These findings identify H1 as a critical regulator of the epigenetic landscape in mammalian cells.
2020-09-09 | GSE152176 | GEO
Project description:H1 linker histones are the most abundant chromatin binding proteins. Their association with chromatin determines the spacing between nucleosomes and enables arrays of nucleosomes to fold into more compact chromatin structures. Mammals express multiple H1 proteins and are able to compensate for the loss of one or even two members by increasing synthesis of other members to maintain a constant H1 to nucleosome stoichiometry. To study the role of H1 in mammalian development, we generated a conditional triple H1 knockout (H1cTKO) mouse strain that enables depletion of H1 in specific cell types. Here, we report on the effects of depleting H1 in adult hematopoietic cells. Deletion of the genes encoding three widely expressed H1 subtypes (H1c, H1d, and H1e) has particularly profound effects on B- and T- lymphocyte development. H1 depletion leads to de-repression of T-cell activation genes, and a shift in T-cells towards effector functions, a process that mimics normal T-cell activation. Comparison of chromatin structure in normal and H1-depleted CD8+ T-cells revealed that H1 binding produces localized chromatin compaction within spatially defined chromatin domains containing above average levels of H1. Reduction of H1 stoichiometry in these regions leads to decreases in H3K27 methylation and increases in H3K36 methylation. In vitro, H1 promotes PRC2-mediated H3K27 methylation and inhibits NSD2-mediated H3K36 methylation. Mechanistically, H1 mediates these opposite effects by promoting physical compaction of the chromatin substrate. These findings identify H1 as a critical regulator of the epigenetic landscape in mammalian cells.
2020-09-09 | GSE141186 | GEO
Project description:H1 linker histones are the most abundant chromatin binding proteins. Their association with chromatin determines the spacing between nucleosomes and enables arrays of nucleosomes to fold into more compact chromatin structures. Mammals express multiple H1 proteins and are able to compensate for the loss of one or even two members by increasing synthesis of other members to maintain a constant H1 to nucleosome stoichiometry. To study the role of H1 in mammalian development, we generated a conditional triple H1 knockout (H1cTKO) mouse strain that enables depletion of H1 in specific cell types. Here, we report on the effects of depleting H1 in adult hematopoietic cells. Deletion of the genes encoding three widely expressed H1 subtypes (H1c, H1d, and H1e) has particularly profound effects on B- and T- lymphocyte development. H1 depletion leads to de-repression of T-cell activation genes, and a shift in T-cells towards effector functions, a process that mimics normal T-cell activation. Comparison of chromatin structure in normal and H1-depleted CD8+ T-cells revealed that H1 binding produces localized chromatin compaction within spatially defined chromatin domains containing above average levels of H1. Reduction of H1 stoichiometry in these regions leads to decreases in H3K27 methylation and increases in H3K36 methylation. In vitro, H1 promotes PRC2-mediated H3K27 methylation and inhibits NSD2-mediated H3K36 methylation. Mechanistically, H1 mediates these opposite effects by promoting physical compaction of the chromatin substrate. These findings identify H1 as a critical regulator of the epigenetic landscape in mammalian cells.
2020-09-09 | GSE141185 | GEO
Project description:H1 linker histones are the most abundant chromatin binding proteins. Their association with chromatin determines the spacing between nucleosomes and enables arrays of nucleosomes to fold into more compact chromatin structures. Mammals express multiple H1 proteins and are able to compensate for the loss of one or even two members by increasing synthesis of other members to maintain a constant H1 to nucleosome stoichiometry. To study the role of H1 in mammalian development, we generated a conditional triple H1 knockout (H1cTKO) mouse strain that enables depletion of H1 in specific cell types. Here, we report on the effects of depleting H1 in adult hematopoietic cells. Deletion of the genes encoding three widely expressed H1 subtypes (H1c, H1d, and H1e) has particularly profound effects on B- and T- lymphocyte development. H1 depletion leads to de-repression of T-cell activation genes, and a shift in T-cells towards effector functions, a process that mimics normal T-cell activation. Comparison of chromatin structure in normal and H1-depleted CD8+ T-cells revealed that H1 binding produces localized chromatin compaction within spatially defined chromatin domains containing above average levels of H1. Reduction of H1 stoichiometry in these regions leads to decreases in H3K27 methylation and increases in H3K36 methylation. In vitro, H1 promotes PRC2-mediated H3K27 methylation and inhibits NSD2-mediated H3K36 methylation. Mechanistically, H1 mediates these opposite effects by promoting physical compaction of the chromatin substrate. These findings identify H1 as a critical regulator of the epigenetic landscape in mammalian cells.
2020-09-09 | GSE141184 | GEO
Project description:H1 linker histones are the most abundant chromatin binding proteins. Their association with chromatin determines the spacing between nucleosomes and enables arrays of nucleosomes to fold into more compact chromatin structures. Mammals express multiple H1 proteins and are able to compensate for the loss of one or even two members by increasing synthesis of other members to maintain a constant H1 to nucleosome stoichiometry. To study the role of H1 in mammalian development, we generated a conditional triple H1 knockout (H1cTKO) mouse strain that enables depletion of H1 in specific cell types. Here, we report on the effects of depleting H1 in adult hematopoietic cells. Deletion of the genes encoding three widely expressed H1 subtypes (H1c, H1d, and H1e) has particularly profound effects on B- and T- lymphocyte development. H1 depletion leads to de-repression of T-cell activation genes, and a shift in T-cells towards effector functions, a process that mimics normal T-cell activation. Comparison of chromatin structure in normal and H1-depleted CD8+ T-cells revealed that H1 binding produces localized chromatin compaction within spatially defined chromatin domains containing above average levels of H1. Reduction of H1 stoichiometry in these regions leads to decreases in H3K27 methylation and increases in H3K36 methylation. In vitro, H1 promotes PRC2-mediated H3K27 methylation and inhibits NSD2-mediated H3K36 methylation. Mechanistically, H1 mediates these opposite effects by promoting physical compaction of the chromatin substrate. These findings identify H1 as a critical regulator of the epigenetic landscape in mammalian cells.
2020-09-09 | GSE153543 | GEO
Project description:Linker histone H1, the key chromatin structural protein facilitating higher order chromatin folding, isan important epigenetic mark and regulator for gene expression and cellular differentiation. However, mechanisms thatregulate H1 binding affinity to chromatin remain elusive. In an attempt to screen functionallong non-coding RNAs(lncRNAs), we designed a cell-type specific score (CTSS) algorithm on the basis of RNA-seq data derived fromcell lines of different origins, which leads to the identification of an epithelium-specific lncRNA designated assmall nucleolar RNA host gene 8 (SNHG8). In epithelial cells, loss of SNHG8d, a major transcriptof SNHG8, remodels the genomic expression profiletowards differentiation. Mechanistically, SNHG8d is localized in the nucleus and manifests stronginteraction withallthe histone H1 variants detected.Loss of SNHG8dleads to increasedH1 binding affinity to chromatinand subsequentchromatin condensationwhichdictates the epithelial differentiation-orientedgenomic expression remodeling.Further analysis proposes that SNHG8d regulates H1-chromatin affinityby competing with linker DNA forhistone H1 binding througha phase-separation mechanism. Thus, our study revealed a lncRNA-conducted mechanismthat sequesters histone H1 from chromatin through phase separation to sequentially regulatechromatin structure, gene expressionandepithelialdifferentiation.
2021-12-31 | GSE151625 | GEO
Project description:Linker histone H1, the key chromatin structural protein facilitating higher order chromatin folding, is an important epigenetic mark and regulator for gene expression and cellular differentiation. However, mechanisms thatregulate H1 binding affinity to chromatin remain elusive. In an attempt to screen functionallong non-coding RNAs(lncRNAs), we designed a cell-type specific score (CTSS) algorithm on the basis of RNA-seq data derived fromcell lines of different origins, which leads to the identification of an epithelium-specific lncRNA designated assmall nucleolar RNA host gene 8 (SNHG8). In epithelial cells, loss of SNHG8d, a major transcriptof SNHG8, remodels the genomic expression profiletowards differentiation. Mechanistically, SNHG8d is localized in the nucleus and manifests stronginteraction withallthe histone H1 variants detected.Loss of SNHG8dleads to increasedH1 binding affinity to chromatinand subsequentchromatin condensationwhichdictates the epithelial differentiation-orientedgenomic expression remodeling.Further analysis proposes that SNHG8d regulates H1-chromatin affinityby competing with linker DNA forhistone H1 binding througha phase-separation mechanism. Thus, our study revealed a lncRNA-conducted mechanismthat sequesters histone H1 from chromatin through phase separation to sequentially regulatechromatin structure, gene expressionandepithelialdifferentiation.
2021-12-31 | GSE151624 | GEO
Project description:PIWI-interacting RNAs (piRNAs) mediate transposable element (TE) silencing at the transcriptional or post-transcriptional level in animal gonads. In the Drosophila ovary, Piwiâ??piRNA complexes (Piwiâ??piRISCs) repress TE transcription by modifying the chromatin state, such as H3K9me3 marks. Here, we demonstrate that Piwi physically interacts with linker histone H1. Depletion of Piwi decreases H1 density on target loci, leading to TE derepression. Loss of H1 results in gain of chromatin accessibility at target loci without affecting H3K9me3 and heterochromatin protein 1a (HP1a) density at the same loci. Piwi-mediated TE silencing also requires HP1a by regulating chromatin accessibility through its association with target loci. Thus, Piwiâ??piRISCs require both H1 and HP1a to repress TEs, and the silencing is correlated with the state of chromatin formation rather than H3K9me3 marks. These findings suggest that Piwiâ??piRISCs regulate the interaction of chromatin components with target loci to maintain silencing of the TE state through the modulation of chromatin accessibility. RNA levels, H1 and H3K9me3 occupancy, chromatin accessibility, and Piwi-associated small RNA levels in ovarian somatic cells (OSC) depleted of piRNA pathway components and H1.
2016-06-30 | E-GEOD-81434 | biostudies-arrayexpress
Project description:Within the cell nucleus, histone H1 is the most mobile histone. Yet, it is regarded as key to the establishment and stability of chromatin higher-order structure. The implication is that chromatin higher-order structure is dynamic, in part due to the mobility of H1. Defining the positions of H1 on chromatin in situ, therefore, represents a challenge. Immunoprecipitation of formaldehyde-fixed and sonicated chromatin, followed by DNA sequencing (xChIP-seq) is traditionally the method for mapping histones onto DNA elements. But since sonication fragmentation precedes ChIP, there is a consequent loss of information about chromatin higher-order structure. A second formaldehyde fixation after antibody binding to intact in situ chromatin, but before sonication (xxChIP-seq), preserves this information and reveals which histone epitopes are inaccessible in situ. In this study, the distribution of two histone H1 variants H1.2 and H1.5 is defined and compared by both xChIP-seq and xxChIP-seq in undifferentiated HL-60/S4 cells, illustrating the influences of preserved chromatin higher-order structure. We have found that xChIP and xxChIP signals are anticorrelated. H1.2 versus H1.5-enrichments were particularly distinct near bound Pol II, SMC3 proteins, as well as domains marked by H3K4me1, H3K9ac, H3K27ac and H3K36me3. H1.5-enriched regions have an average nucleosome repeat length NRL=184 bp, as opposed to 190 bp for H1.2-enriched regions. We have also studied the distribution of H1 variants with respect to DNA methylation. Most changes of DNA methylation during differentiation appear within ~60bp from the nucleosome entry/exit and are preferably associated with H1.2-bound nucleosomes, whereas H1.5 histones are depleted from CpGs. Our results suggest that different physical packing of nucleosomes may exist in H1.2- versus H1.5-enriched areas, characterized by differential H1 epitope exposure as assessed by xChIP and xxChIP.
2020-06-14 | GSE136264 | GEO
Project description:Linker histones are highly abundant chromatin-associated proteins with well-established structural roles in chromatin and as general transcriptional repressors. In addition, it has been long proposed that histone H1 exerts context-specific effects on gene expression. Here, we have identified a new function of histone H1 in chromatin structure and transcription using a range of genomic approaches. We show that histone H1-depleted cells accumulate nascent non-coding RNAs on chromatin, suggesting that histone H1 prevents non-coding RNA transcription and regulates non-coding transcript turnover on chromatin. Accumulated non-coding transcripts have reduced levels of m6A modification causing replication-transcription conflicts. Accordingly, altering the m6A RNA methylation pathway rescues the replicative phenotype of H1 loss. This work unveils unexpected regulatory roles of histone H1 on non-coding RNA turnover and m6A deposition, highlighting the intimate relationship between chromatin conformation, RNA metabolism and DNA replication to maintain genome performance.
2022-09-13 | GSE166426 | GEO