Hippo Signaling regulates Brahma to influence intestinal stem cell proliferation

Brahma (Brm) complex is a SWI/SNF-related chromatin remodeling complex required to correctly maintain proper states of gene expression through ATP-dependent effects on chromatin structure. Recently, researchers from Chinese Academy of Sciences (CAS) reveal that Brm complex, regulated by Hippo signaling, is required for intestinal stem cell (ISC) proliferation. They identified that Hippo signaling induces caspase-dependent cleavage of Brm to regulate the protein level of Brm.

Under the supervision of Prof. ZHANG Lei and Prof. ZHAO Yun at the Shanghai Institute of Biochemistry & Cell Biology, CAS, Dr. JIN Yunyun and her colleagues uncovered that Brm complex is required for ISC proliferation and damage-induced midgut regeneration in a lineage-specific manner. Brm is the ATPase subunit of Brm complex. They observed that Drosophila ISCs and enteroblasts (EBs) exhibited high levels of Brm protein, whereas, without Brm, ISC proliferation and differentiation were impaired. They also provided evidence that the Brm complex participates in ISC proliferation induced by Scalloped-Yorkie transcriptional complex. Further, they demonstrated that Hippo signaling directly restricted ISC proliferation by regulating Brm protein levels by inducing caspase-dependent cleavage of Brm.

This study entitled “Brahma is essential for Drosophila intestinal stem cell proliferation and regulated by Hippo signaling” was published online in the eLife on Oct 15^th, 2013. It was supported by grants from the Ministry of Science and Technology of China, the National Natural Science Foundation of China, and the “Strategic Priority Research Program” of the Chinese Academy of Sciences.

Brahma plays an important role in Drosophila ISC proliferation and is regulated by Hippo signaling