scholarly journals Brahma is essential for Drosophila intestinal stem cell proliferation and regulated by Hippo signaling

eLife ◽  
2013 ◽  
Vol 2 ◽  
Author(s):  
Yunyun Jin ◽  
Jinjin Xu ◽  
Meng-Xin Yin ◽  
Yi Lu ◽  
Lianxin Hu ◽  
...  

Chromatin remodeling processes are among the most important regulatory mechanisms in controlling cell proliferation and regeneration. Drosophila intestinal stem cells (ISCs) exhibit self-renewal potentials, maintain tissue homeostasis, and serve as an excellent model for studying cell growth and regeneration. In this study, we show that Brahma (Brm) chromatin-remodeling complex is required for ISC proliferation and damage-induced midgut regeneration in a lineage-specific manner. ISCs and enteroblasts exhibit high levels of Brm proteins; and without Brm, ISC proliferation and differentiation are impaired. Importantly, the Brm complex participates in ISC proliferation induced by the Scalloped–Yorkie transcriptional complex and that the Hippo (Hpo) signaling pathway directly restricted ISC proliferation by regulating Brm protein levels by inducing caspase-dependent cleavage of Brm. The cleavage resistant form of Brm protein promoted ISC proliferation. Our findings highlighted the importance of Hpo signaling in regulating epigenetic components such as Brm to control downstream transcription and hence ISC proliferation.

2005 ◽  
Vol 25 (20) ◽  
pp. 9016-9027 ◽  
Author(s):  
Jianguang Chen ◽  
Trevor K. Archer

ABSTRACT The mammalian SWI/SNF chromatin remodeling complex, whose function is of critical importance in transcriptional regulation, contains approximately 10 protein components. The expression levels of the core SWI/SNF subunits, including BRG1/Brm, BAF155, BAF170, BAF60, hSNF/Ini1, and BAF57, are stoichiometric, with few to no unbound molecules in the cell. Here we report that exogenous expression of the wild type or certain deletion mutants of BAF57, a key subunit that mediates the interaction between the remodeling complex and transcription factors, results in diminished expression of endogenous BAF57. This down-regulation process is mediated by an increase in proteasome-dependent degradation of the BAF57 protein. Furthermore, the protein levels of BAF155/170 dictate the maximum cellular amount of BAF57. We mapped the domains responsible for the interaction between BAF57 and BAF155 and demonstrated that protein-protein interactions between them play an important role in this regulatory process. These findings provide insights into the physiological mechanisms responsible for maintaining the proper stoichiometric levels of the protein components comprising multimeric enzyme complexes.


2020 ◽  
Vol 21 (14) ◽  
pp. 4925
Author(s):  
Estephania Zluhan-Martínez ◽  
Vadim Pérez-Koldenkova ◽  
Martha Verónica Ponce-Castañeda ◽  
María de la Paz Sánchez ◽  
Berenice García-Ponce ◽  
...  

The Retinoblastoma protein (pRb) is a key cell cycle regulator conserved in a wide variety of organisms. Experimental analysis of pRb’s functions in animals and plants has revealed that this protein participates in cell proliferation and differentiation processes. In addition, pRb in animals and its orthologs in plants (RBR), are part of highly conserved protein complexes which suggest the possibility that analogies exist not only between functions carried out by pRb orthologs themselves, but also in the structure and roles of the protein networks where these proteins are involved. Here, we present examples of pRb/RBR participation in cell cycle control, cell differentiation, and in the regulation of epigenetic changes and chromatin remodeling machinery, highlighting the similarities that exist between the composition of such networks in plants and animals.


1998 ◽  
Vol 333 (3) ◽  
pp. 645-654 ◽  
Author(s):  
Judit GARRIGA ◽  
Ana LIMÓN ◽  
Xavier MAYOL ◽  
Sushil G. RANE ◽  
Jeffrey H. ALBRECHT ◽  
...  

In the present study we have analysed the regulation of pocket protein expression and post-transcriptional modifications on cell proliferation and differentiation, both in vivo and in vitro. There are marked changes in pocket protein levels during these transitions, the most striking differences being observed between p130 and p107. The mechanisms responsible for regulating pocket protein levels seem to be dependent on both cell type and pocket protein, in addition to their dependence on the cell growth status. Changes in retinoblastoma protein and p107 levels are independent of their state of phosphorylation. However, whereas p130 phosphorylation to forms characteristic of quiescent/differentiated cells results in the accumulation of p130 protein, phosphorylation of p130 to one or more forms characteristic of cycling cells is accompanied by down-regulation of its protein levels. We also show here that the phosphorylation status and protein levels of p130 and p107 are regulated in vivo as in cultured cells. In vivo, changes in p130 forms are correlated with changes in E2F complexes. Moreover, the modulation of p130 and p107 status during cell differentiation in vitro is consistent with the patterns of protein expression and phosphorylation status found in mouse tissues. Thus in addition to the direct disruption of pocket protein/E2F complexes induced by cyclin/cyclin-dependent kinase, the results we report here indicate that the differential modulation of pocket protein levels constitutes a major mechanism that regulates the pool of each pocket protein that is accessible to E2F and/or other transcription factors.


Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1600
Author(s):  
Longlong Zhang ◽  
Maosen Ye ◽  
Liang Zhu ◽  
Jingmei Cha ◽  
Chaocui Li ◽  
...  

The ubiquitin E3 ligase RNF220 and its co-factor ZC4H2 are required for multiple neural developmental processes through different targets, including spinal cord patterning and the development of the cerebellum and the locus coeruleus. Here, we explored the effects of loss of ZC4H2 and RNF220 on the proliferation and differentiation of neural stem cells (NSCs) derived from mouse embryonic cortex. We showed that loss of either ZC4H2 or RNF220 inhibits the proliferation and promotes the differentiation abilities of NSCs in vitro. RNA-Seq profiling revealed 132 and 433 differentially expressed genes in the ZC4H2−/− and RNF220−/− NSCs, compared to wild type (WT) NSCs, respectively. Specifically, Cend1, a key regulator of cell cycle exit and differentiation of neuronal precursors, was found to be upregulated in both ZC4H2−/− and RNF220−/− NSCs at the mRNA and protein levels. The targets of Cend1, such as CyclinD1, Notch1 and Hes1, were downregulated both in ZC4H2−/− and RNF220−/− NSCs, whereas p53 and p21 were elevated. ZC4H2−/− and RNF220−/− NSCs showed G0/G1 phase arrest compared to WT NSCs in cell cycle analysis. These results suggested that ZC4H2 and RNF220 are likely involved in the regulation of neural stem cell proliferation and differentiation through Cend1.


2021 ◽  
pp. 67-122
Author(s):  
Rūta Navakauskienė ◽  
Dalius Navakauskas ◽  
Veronika Borutinskaitė ◽  
Dalius Matuzevičius

2019 ◽  
Vol 484 (5) ◽  
pp. 633-636
Author(s):  
Eu. V. Tatarskiy ◽  
G. P. Georgiev ◽  
N. V. Soshnikova

The PBAF(SWI/SNF) multiprotein complex, which changes the chromatin structure, is widely involved in the regulation of eukaryotic gene expression. A specific component of this complex is the PHF10 protein, which is involved in recruiting this complex to chromatin. We showed that the PHF10 expression in cells of different lines is activated by the c-MYC oncogene. Since PHF10 stimulates cell proliferation, its c-MYC-dependent activation in cancer cells should lead to an increase in their proliferation rate.


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