Similar Datasets
Project description:Trimethylated histone H3 lysine 27 (H3K27me3) regulates gene repression, cell-fate determination and differentiation. We report that a conserved bromo-adjacent homology (BAH) module of BAHCC1 (BAHCC1BAH) 'recognizes' H3K27me3 specifically and enforces silencing of H3K27me3-demarcated genes in mammalian cells. Biochemical, structural and integrated chromatin immunoprecipitation-sequencing-based analyses demonstrate that direct readout of H3K27me3 by BAHCC1 is achieved through a hydrophobic trimethyl-L-lysine-binding 'cage' formed by BAHCC1BAH, mediating colocalization of BAHCC1 and H3K27me3-marked genes. BAHCC1 is highly expressed in human acute leukemia and interacts with transcriptional corepressors. In leukemia, depletion of BAHCC1, or disruption of the BAHCC1BAH-H3K27me3 interaction, causes derepression of H3K27me3-targeted genes that are involved in tumor suppression and cell differentiation, leading to suppression of oncogenesis. In mice, introduction of a germline mutation at Bahcc1 to disrupt its H3K27me3 engagement causes partial postnatal lethality, supporting a role in development. This study identifies an H3K27me3-directed transduction pathway in mammals that relies on a conserved BAH 'reader'.
| S-EPMC8330957 | biostudies-literature
Project description:Tri-methylation of histone H3 lysine 27 (H3K27me3) regulates transcriptional repression, cell-fate determination and differentiation. We report that a conserved Bromo-Adjacent Homology (BAH) module harbored within BAHCC1, a previously uncharacterized chromatin regulator, ‘recognizes’ H3K27me3 specifically and enforces silencing of H3K27me3-demarcated genes in mammalian cells. Biochemical, structural and ChIP-seq-based analyses demonstrate that direct ‘readout’ of H3K27me3 by BAHCC1 is achieved through a hydrophobic trimethyl-lysine-binding ‘cage’ formed by the BAH domain, mediating co-localization of BAHCC1 and H3K27me3-marked genes. BAHCC1 is significantly overexpressed in human acute leukemia and biochemically, BAHCC1 interacts with repressors SAP30BP and HDAC. In acute leukemia, depletion of BAHCC1, or disruption of the BAHCC1 BAH-mediated ‘readout’ of H3K27me3, causes de-repression of H3K27me3-targeted genes that are involved in tumor suppression and cell differentiation, leading to the suppressed tumor growth. In mice, introduction of a germ-line mutation at Bahcc1 to disrupt its H3K27me3 engagement causes postnatal lethality, supporting a role of this pathway in development. Collectively, this study unveils a novel H3K27me3-directed transduction pathway in mammal cells that relies on a conserved BAH ‘reader’, deregulation of which contributes to oncogenesis.
2020-09-28 | GSE151577 | GEO
Project description:Tri-methylation of histone H3 lysine 27 (H3K27me3) regulates transcriptional repression, cell-fate determination and differentiation. We report that a conserved Bromo-Adjacent Homology (BAH) module harbored within BAHCC1, a previously uncharacterized chromatin regulator, ‘recognizes’ H3K27me3 specifically and enforces silencing of H3K27me3-demarcated genes in mammalian cells. Biochemical, structural and ChIP-seq-based analyses demonstrate that direct ‘readout’ of H3K27me3 by BAHCC1 is achieved through a hydrophobic trimethyl-lysine-binding ‘cage’ formed by the BAH domain, mediating co-localization of BAHCC1 and H3K27me3-marked genes. BAHCC1 is significantly overexpressed in human acute leukemia and biochemically, BAHCC1 interacts with repressors SAP30BP and HDAC. In acute leukemia, depletion of BAHCC1, or disruption of the BAHCC1 BAH-mediated ‘readout’ of H3K27me3, causes de-repression of H3K27me3-targeted genes that are involved in tumor suppression and cell differentiation, leading to the suppressed tumor growth. In mice, introduction of a germ-line mutation at Bahcc1 to disrupt its H3K27me3 engagement causes postnatal lethality, supporting a role of this pathway in development. Collectively, this study unveils a novel H3K27me3-directed transduction pathway in mammal cells that relies on a conserved BAH ‘reader’, deregulation of which contributes to oncogenesis.
2020-09-28 | GSE151575 | GEO
Project description:Tri-methylation of histone H3 lysine 27 (H3K27me3) regulates transcriptional repression, cell-fate determination and differentiation. We report that a conserved Bromo-Adjacent Homology (BAH) module harbored within BAHCC1, a previously uncharacterized chromatin regulator, ‘recognizes’ H3K27me3 specifically and enforces silencing of H3K27me3-demarcated genes in mammalian cells. Biochemical, structural and ChIP-seq-based analyses demonstrate that direct ‘readout’ of H3K27me3 by BAHCC1 is achieved through a hydrophobic trimethyl-lysine-binding ‘cage’ formed by the BAH domain, mediating co-localization of BAHCC1 and H3K27me3-marked genes. BAHCC1 is significantly overexpressed in human acute leukemia and biochemically, BAHCC1 interacts with repressors SAP30BP and HDAC. In acute leukemia, depletion of BAHCC1, or disruption of the BAHCC1 BAH-mediated ‘readout’ of H3K27me3, causes de-repression of H3K27me3-targeted genes that are involved in tumor suppression and cell differentiation, leading to the suppressed tumor growth. In mice, introduction of a germ-line mutation at Bahcc1 to disrupt its H3K27me3 engagement causes postnatal lethality, supporting a role of this pathway in development. Collectively, this study unveils a novel H3K27me3-directed transduction pathway in mammal cells that relies on a conserved BAH ‘reader’, deregulation of which contributes to oncogenesis.
2020-09-28 | GSE151574 | GEO
Project description:Tri-methylation of histone H3 lysine 27 (H3K27me3) regulates transcriptional repression, cell-fate determination and differentiation. We report that a conserved Bromo-Adjacent Homology (BAH) module harbored within BAHCC1, a previously uncharacterized chromatin regulator, ‘recognizes’ H3K27me3 specifically and enforces silencing of H3K27me3-demarcated genes in mammalian cells. Biochemical, structural and ChIP-seq-based analyses demonstrate that direct ‘readout’ of H3K27me3 by BAHCC1 is achieved through a hydrophobic trimethyl-lysine-binding ‘cage’ formed by the BAH domain, mediating co-localization of BAHCC1 and H3K27me3-marked genes. BAHCC1 is significantly overexpressed in human acute leukemia and biochemically, BAHCC1 interacts with repressors SAP30BP and HDAC. In acute leukemia, depletion of BAHCC1, or disruption of the BAHCC1 BAH-mediated ‘readout’ of H3K27me3, causes de-repression of H3K27me3-targeted genes that are involved in tumor suppression and cell differentiation, leading to the suppressed tumor growth. In mice, introduction of a germ-line mutation at Bahcc1 to disrupt its H3K27me3 engagement causes postnatal lethality, supporting a role of this pathway in development. Collectively, this study unveils a novel H3K27me3-directed transduction pathway in mammal cells that relies on a conserved BAH ‘reader’, deregulation of which contributes to oncogenesis.
2020-09-28 | GSE151573 | GEO
Project description:BAHCC1 couples H3K27me3 to gene silencing and tumorigenesis via a conserved BAH module
| PRJNA636389 | ENA
Project description:BAHCC1 couples H3K27me3 to gene silencing and tumorigenesis via a conserved BAH module [GW760_K27me3_ChIPseq]
| PRJNA636398 | ENA
Project description:BAHCC1 couples H3K27me3 to gene silencing and tumorigenesis via a conserved BAH module [BAHCC1_KD_k27me3_293_ChIPseq]
| PRJNA636394 | ENA
Project description:BAHCC1 couples H3K27me3 to gene silencing and tumorigenesis via a conserved BAH module [Gw760_E2aPbx1_mouse_Rnaseq]
| PRJNA636395 | ENA
Project description:Trimethylation of histone H3 lysine 27 (H3K27me3) is important for gene silencing and imprinting, (epi)genome organization and organismal development. In a prevalent model, the functional readout of H3K27me3 in mammalian cells is achieved through the H3K27me3-recognizing chromodomain harbored within the chromobox (CBX) component of canonical Polycomb repressive complex 1 (cPRC1), which induces chromatin compaction and gene repression. Here, we report that binding of H3K27me3 by a Bromo Adjacent Homology (BAH) domain harbored within BAH domain-containing protein 1 (BAHD1) is required for overall BAHD1 targeting to chromatin and for optimal repression of the H3K27me3-demarcated genes in mammalian cells. Disruption of direct interaction between BAHD1BAH and H3K27me3 by point mutagenesis leads to chromatin remodeling, notably, increased histone acetylation, at its Polycomb gene targets. Mice carrying an H3K27me3-interaction-defective mutation of Bahd1BAH causes marked embryonic lethality, showing a requirement of this pathway for normal development. Altogether, this work demonstrates an H3K27me3-initiated signaling cascade that operates through a conserved BAH 'reader' module within BAHD1 in mammals.
| S-EPMC8096256 | biostudies-literature