UNASSIGNED: Safeguarding the proteome is central to the health of the cell. In multi- @entity33867 , the composition of the proteome, and by extension, protein-folding requirements, varies between cells. In agreement, chaperone network composition differs between tissues. Here, we ask how chaperone expression is regulated in a cell type-specific manner and whether cellular differentiation affects chaperone expression. Our bioinformatics analyses show that the myogenic transcription factor @entity68846 (MyoD) can bind to the promoters of chaperone genes expressed or required for the folding of muscle proteins. To test this experimentally, we employed @entity68846 myogenic potential to genetically modulate cellular differentiation of @entity2199 embryonic cells by ectopically expressing @entity68846 in all cells of the embryo and monitoring chaperone expression. We found that @entity68846 -dependent myogenic conversion specifically induced the expression of putative @entity68846 -regulated chaperones in differentiating muscle cells. Moreover, disrupting the putative @entity68846 -binding sites on ubiquitously expressed @entity68847 (Hsp90) and muscle-enriched hsp-12.2(sHsp) promoters abolished their myogenic-dependent expression. Disrupting @entity68846 function in muscle cells reduced the expression of putative @entity68846 -regulated chaperones and compromised muscle @entity5085 during and after embryogenesis. In turn, we found that modulating the expression of muscle chaperones disrupted the folding and assembly of muscle proteins and thus, myogenesis. Moreover, muscle-specific over-expression of the DNAJB6 homolog @entity68848 , a @entity17325 -associated chaperone, disrupted the muscle chaperone network and exposed synthetic motility defects. We propose that cellular differentiation could establish a @entity5085 network dedicated to the folding and maintenance of the muscle proteome. Such cell-specific @entity5085 networks can explain the selective vulnerability that many diseases of protein misfolding exhibit even when the misfolded protein is ubiquitously expressed.

A Differentiation Transcription Factor Establishes Muscle-Specific Proteostasis in XXXX .

@entity68848 :: ('175745(Tax:6239)', 'Gene') :: ['DNJ-24'] @entity2199 :: ('6239', 'Species') :: ['Caenorhabditis elegans'] @entity68847 :: ('179971(Tax:6239)', 'Gene') :: ['daf-21'] @entity5085 :: ('MESH:D057165', 'Disease') :: ['proteostasis'] @entity33867 :: ('131567', 'Species') :: ['cellular organisms'] @entity17325 :: ('MESH:D049288', 'Disease') :: ['limb-girdle muscular dystrophy'] @entity68846 :: ('173788(Tax:6239)', 'Gene') :: ['HLH-1']
@entity2199 :: (6239,Species) :: ['Caenorhabditis elegans']
