Project description:Induction of lineage-specific gene programs are strongly influenced by alterations in local chromatin architecture. However, key players that impact this genome reorganization remain largely unknown. Here, we report that removal of special AT-rich binding protein 2 (SATB2), a nuclear protein known to bind matrix attachment regions, is a key event in initiating myogenic differentiation. Deletion of myoblast SATB2 in vitro initiates chromatin remodeling and accelerates differentiation, while in vivo ablation depletes the muscle progenitor pool. Genome wide analysis indicates that SATB2 binding influences both chromatin loop and sub-TAD domain formation. These chromatin changes are both repressive and inductive, as loss of SATB2 leads to expression of differentiation regulatory factors and inhibition of genes that impair this process. Finally, we noted that the differentiation-specific decline in SATB2 protein is dependent on a caspase 7-mediated cleavage event. Taken together, this study demonstrates that temporal control of SATB2 protein is critical for shaping the chromatin environment and coordinating the myogenic differentiation program
Project description:Induction of lineage-specific gene programs are strongly influenced by alterations in local chromatin architecture. However, key players that impact this genome reorganization remain largely unknown. Here, we report that removal of special AT-rich binding protein 2 (SATB2), a nuclear protein known to bind matrix attachment regions, is a key event in initiating myogenic differentiation. Deletion of myoblast SATB2 in vitro initiates chromatin remodeling and accelerates differentiation, while in vivo ablation depletes the muscle progenitor pool. Genome wide analysis indicates that SATB2 binding influences both chromatin loop and sub-TAD domain formation. These chromatin changes are both repressive and inductive, as loss of SATB2 leads to expression of differentiation regulatory factors and inhibition of genes that impair this process. Finally, we noted that the differentiation-specific decline in SATB2 protein is dependent on a caspase 7-mediated cleavage event. Taken together, this study demonstrates that temporal control of SATB2 protein is critical for shaping the chromatin environment and coordinating the myogenic differentiation program
Project description:Induction of lineage-specific gene programs are strongly influenced by alterations in local chromatin architecture. However, key players that impact this genome reorganization remain largely unknown. Here, we report that removal of special AT-rich binding protein 2 (SATB2), a nuclear protein known to bind matrix attachment regions, is a key event in initiating myogenic differentiation. Deletion of myoblast SATB2 in vitro initiates chromatin remodeling and accelerates differentiation, while in vivo ablation depletes the muscle progenitor pool. Genome wide analysis indicates that SATB2 binding influences both chromatin loop and sub-TAD domain formation. These chromatin changes are both repressive and inductive, as loss of SATB2 leads to expression of differentiation regulatory factors and inhibition of genes that impair this process. Finally, we noted that the differentiation-specific decline in SATB2 protein is dependent on a caspase 7-mediated cleavage event. Taken together, this study demonstrates that temporal control of SATB2 protein is critical for shaping the chromatin environment and coordinating the myogenic differentiation program
Project description:The induction of lineage-specific gene programs are strongly influenced by alterations in local chromatin architecture. However, key players that impact this genome reorganization remain largely unknown. Here, we report that the removal of the special AT-rich binding protein 2 (SATB2), a nuclear protein known to bind matrix attachment regions, is a key event in initiating myogenic differentiation. The deletion of myoblast SATB2 in vitro initiates chromatin remodeling and accelerates differentiation, which is dependent on the caspase 7-mediated cleavage of SATB2. A genome-wide analysis indicates that SATB2 binding within chromatin loops and near anchor points influences both loop and sub-TAD domain formation. Consequently, the chromatin changes that occur with the removal of SATB2 lead to the derepression of differentiation-inducing factors while also limiting the expression of genes that inhibit this cell fate change. Taken together, this study demonstrates that the temporal control of the SATB2 protein is critical in shaping the chromatin environment and coordinating the myogenic differentiation program.
Project description:This data identifies the cleavage fragment of an in vitro reaction between recombinant, active caspase 7 and recombinant SATB2. The data confirms that this fragment is indeed a part of SATB2 and this information was used to further our investigation into the role SATB2 in mammalian skeletal muscle satellite cells.
Project description:Induction of lineage-specific gene programs are strongly influenced by alterations in local chromatin architecture. However, key players that impact this genome reorganization remain largely unknown. In our associated paper, we found that the removal of special AT-rich binding protein 2 (SATB2), a nuclear protein that binds matrix attachment regions, is a key event in initiating myogenic differentiation. This study included ChIP-seq analyses to assess the genetic binding sites of SATB2 prior to differentiation and categorize their respective roles within the cell. Furthermore, transcriptome analyses using RNA-seq was conducted on C2C12 cells treated with control siRNA and siRNA against SATB2 prior to differentiation. This was done to assess the changes in transcript expression following the loss of SATB2.