Signaling Pathways Associated with Chromatin Remodeling
Numerous signaling cascades converge on the nucleus during development to direct chromatin remodeling that influences transcriptional regulation. For example, proper TGFβ signaling gradients are essential for cellular viability and differentiation. Activation of TGFβ receptors located at the cell surface catalyzes a phosphorylation cascade that leads to SMAD protein interactions in the cytoplasm and their subsequent relocation to the nucleus. Interestingly, high cell density of various cell lines prevented SMAD translocation to the nucleus in vitro, suggesting extrinsic factors in addition to morphogen gradients that may contribute to TGFβ signaling.
The SMAD1/5/8 complex is activated via BMP GDF ligands, while Activin/NODAL associated SMAD2/3 complex. Once transported inside the nucleus, the SMAD complex interacts with additional transcription factors to bind the SMAD DNA binding element and activate target gene ex
WNT/β catenin signaling has also been show to direct chromatin remodeling. WNT ligands bind to Frizzeled and LRP receptors on the cell surface, allows β catenin’s translocation to the nucleus where it interacts with TCF/LEF transcription factors to promote gene activation. In addition to an overlap between GATA1/2 and SMAD1 previously mentioned, Trompouki and colleagues also found that TCF7L2 binding overlapped with SMAD1/GATA1/2 binding, suggesting an overlap in WNT and BMP signaling pathways. In some scenarios, the C terminus of β catenin directly interacts with the HMTs MLL1/MLL2 to stimulate H3K4 methylation, which leads to ex