The Roles of Hippo Signaling Transducers Yap and Taz in Chromatin Remodeling

Abstract

Hippo signaling controls cellular processes that ultimately impact organogenesis and homeostasis. Consequently, disease states including cancer can emerge when signaling is deregulated. The major pathway transducers Yap and Taz require cofactors to impart transcriptional control over target genes. Research into Yap/Taz-mediated epigenetic modifications has revealed their association with chromatin-remodeling complex proteins as a means of altering chromatin structure, therefore affecting accessibility and activity of target genes. Specifically, Yap/Taz have been found to associate with factors of the GAGA, Ncoa6, Mediator, Switch/sucrose nonfermentable (SWI/SNF), and Nucleosome Remodeling and Deacetylase (NuRD) chromatin-remodeling complexes to alter the accessibility of target genes. This review highlights the different mechanisms by which Yap/Taz collaborate with other factors to modify DNA packing at specific loci to either activate or repress target gene transcription.

TAZ Represses the Neuronal Commitment of Neural Stem Cells

“…At this time, the specific factors that participate in the separation of both programs are still a matter of study [ 55 , 56 ]. Recent studies have suggested that the YAP and TAZ effectors for the WNT and Hippo pathways mediate epigenetic modifications in association with the chromatin-remodeling proteins, therefore affecting accessibility and activity of target genes [ 57 ]. Considering that the WNT and Hippo pathways participate in the maintenance of the NSPCs pool [ 58 ], in this study, we investigated the specific role of TAZ in neurogenesis.…”

Role of YAP/TAZ in Cell Lineage Fate Determination and Related Signaling Pathways

“…Lastly, a newly emerging research frontier on how YAP/TAZ modulate stem cell function, are their novel roles in effecting epigenetic modifications to chromatin structure ( Hillmer and Link, 2019 ) and post-transcriptional miRNA processing ( Chaulk et al, 2014 ; Mori et al, 2014 ). Epigenetic modifications mediated by YAP/TAZ are effected by their association with chromatin-remodeling complexes proteins such as Nucleosome Remodeling and Deacetylase (NuRD), Switch/sucrose non-fermentable (SWI/SNF), Ncoa6, Mediator, and GAGA, which in turn influence the accessibility and activity of various target genes via alterations to chromatin structure ( Hillmer and Link, 2019 ). Post-transcriptional processing of miRNA is known to be regulated by YAP/TAZ via their binding interactions with p72 (DDX17) that regulates Microprocessor activity ( Mori et al, 2014 ), as well as by modulation of Dicer activity through the LIN28/Let-7 axis ( Chaulk et al, 2014 ).…”

HPV E6 Protein Associated SOX21-AS1 Promotes YAP/TAZ Activation by Attenuating YAP1 Ubiquitination in Human Cervical Cancer

“…YAP1 itself has no transcriptional activity, it is a transcriptional co-activator when combined with its TAZ and TEADs [19]. All of these three components are indispensable for downstream transcripts boost, therefore, the nuclear translocation of YAP1 is the key regulatory manner, and this process is blocked by Hippo pathway when it is in the"on"state [20,21]. The"on"state of the Hippo pathway is considered as tumor suppressive functions, since amounts of researches revealed its"on" state is capable of inhibiting cell proliferation, promoting apoptosis and regulating stem/progenitor cell expansion [20,21].…”