Project description:Structural Maintenance of chromosomes (SMC) complexes, cohesin and condensins, have been named after their roles during meiosis and mitosis. Recent data in mammalian cells and Drosophila have described the additional role of cohesin for genome folding into loops and domains during interphase. However, determinants of genome folding in holocentric species remain unclear. Using high resolution chromosome conformation capture, we show that overlapping large-scale nuclear localization and small-scale epigenomic states compartmentalize the C. elegans genome. By systematically and acutely inactivating each SMC complex, we observe that in contrast to other studied systems, cohesin creates small loops, while condensin I has a major role in genome folding: its inactivation causes genome-wide decompaction, chromosome mixing, loss of loops and TAD structures and reinforcement of fine-scale epigenomic compartments. Counter-intuitively, removal of condensin I and its X-specific variant condensin IDC from the X chromosomes led to the formation of a loop compartment coinciding with a subset of previously characterized loading sites for condensin IDC and bound by the X-targeting complex SDC. While transcriptional changes were limited for all autosomes upon cohesin and condensin II inactivation, removal of condensin I/IDC from the X chromosome led to transcriptional up-regulation of X-linked genes demonstrating that a sustained role for condensin IDC in gene regulation. Finally, while condensin I inactivation leads to reduced lifespan, we show that this reduction is due to X-specific gene upregulation rather than global genome decompaction.
Project description:Structural Maintenance of chromosomes (SMC) complexes, cohesin and condensins, have been named after their roles during meiosis and mitosis. Recent data in mammalian cells and Drosophila have described the additional role of cohesin for genome folding into loops and domains during interphase. However, determinants of genome folding in holocentric species remain unclear. Using high resolution chromosome conformation capture, we show that overlapping large-scale nuclear localization and small-scale epigenomic states compartmentalize the C. elegans genome. By systematically and acutely inactivating each SMC complex, we observe that in contrast to other studied systems, cohesin creates small loops, while condensin I has a major role in genome folding: its inactivation causes genome-wide decompaction, chromosome mixing, loss of loops and TAD structures and reinforcement of fine-scale epigenomic compartments. Counter-intuitively, removal of condensin I and its X-specific variant condensin IDC from the X chromosomes led to the formation of a loop compartment coinciding with a subset of previously characterized loading sites for condensin IDC and bound by the X-targeting complex SDC. While transcriptional changes were limited for all autosomes upon cohesin and condensin II inactivation, removal of condensin I/IDC from the X chromosome led to transcriptional up-regulation of X-linked genes demonstrating that a sustained role for condensin IDC in gene regulation. Finally, while condensin I inactivation leads to reduced lifespan, we show that this reduction is due to X-specific gene upregulation rather than global genome decompaction.
Project description:Structural Maintenance of chromosomes (SMC) complexes, cohesin and condensins, have been named after their roles during meiosis and mitosis. Recent data in mammalian cells and Drosophila have described the additional role of cohesin for genome folding into loops and domains during interphase. However, determinants of genome folding in holocentric species remain unclear. Using high resolution chromosome conformation capture, we show that overlapping large-scale nuclear localization and small-scale epigenomic states compartmentalize the C. elegans genome. By systematically and acutely inactivating each SMC complex, we observe that in contrast to other studied systems, cohesin creates small loops, while condensin I has a major role in genome folding: its inactivation causes genome-wide decompaction, chromosome mixing, loss of loops and TAD structures and reinforcement of fine-scale epigenomic compartments. Counter-intuitively, removal of condensin I and its X-specific variant condensin IDC from the X chromosomes led to the formation of a loop compartment coinciding with a subset of previously characterized loading sites for condensin IDC and bound by the X-targeting complex SDC. While transcriptional changes were limited for all autosomes upon cohesin and condensin II inactivation, removal of condensin I/IDC from the X chromosome led to transcriptional up-regulation of X-linked genes demonstrating that a sustained role for condensin IDC in gene regulation. Finally, while condensin I inactivation leads to reduced lifespan, we show that this reduction is due to X-specific gene upregulation rather than global genome decompaction.
Project description:Condensins are multi-subunit protein complexes that regulate chromosome structure throughout cell-cycle. Metazoans contain two types of condensin complexes (I and II) with essential and distinct functions. In C. elegans a third type of condensin (IDC) functions as part of the X chromosome dosage compensation complex1,2. We mapped genome-wide binding sites of the three condensin types in C. elegans embryos. Characteristics of condensin binding are similar between condensin types. ChIP-seq profiles of C. elegans subunits of the three condensins in 3-6 replicates from mixed stage embryos, controls are included, and RNA-Seq profiles of C. elegans in 5 replicates from mixed staged embryos. Additionally, ChIP-seq profiles of the condensin II subunit KLE-2 in 6 replicates from L3 with controls, and RNA-Seq profiles of KLE-2 mutants in 3 replicates each from L3.
Project description:Condensins are multi-subunit protein complexes that regulate chromosome structure throughout cell-cycle. Metazoans contain two types of condensin complexes (I and II) with essential and distinct functions. In C. elegans a third type of condensin (IDC) functions as part of the X chromosome dosage compensation complex1,2. We mapped genome-wide binding sites of the three condensin types in C. elegans embryos. Characteristics of condensin binding are similar between condensin types.
Project description:Ribo-zero RNAseq experiments were carried out with mouse distal colon DSS Colitis model of genetically engineered mice. For each mouse line for: Gpsm3 (3% DSS), Aif1 (3% DSS), Nckap1l (Hem1), Dock2 (3% DSS), Dok3 (3.5% DSS) DSS treatment for five days followed by water for 5 days, (7 days for Nckap1l). Tissue was collected at Day 10 (Day 12 for Nckap1l (HEM1)).