A single transcription factor is sufficient to induce and maintain secretory cell architecture.

Abstract:

:We hypothesized that basic helix-loop-helix (bHLH) MIST1 (BHLHA15) is a "scaling factor" that universally establishes secretory morphology in cells that perform regulated secretion. Here, we show that targeted deletion of MIST1 caused dismantling of the secretory apparatus of diverse exocrine cells. Parietal cells (PCs), whose function is to pump acid into the stomach, normally lack MIST1 and do not perform regulated secretion. Forced expression of MIST1 in PCs caused them to expand their apical cytoplasm, rearrange mitochondrial/lysosome trafficking, and generate large secretory granules. Mist1 induced a cohort of genes regulated by MIST1 in multiple organs but did not affect PC function. MIST1 bound CATATG/CAGCTG E boxes in the first intron of genes that regulate autophagosome/lysosomal degradation, mitochondrial trafficking, and amino acid metabolism. Similar alterations in cell architecture and gene expression were also caused by ectopically inducing MIST1 in vivo in hepatocytes. Thus, MIST1 is a scaling factor necessary and sufficient by itself to induce and maintain secretory cell architecture. Our results indicate that, whereas mature cell types in each organ may have unique developmental origins, cells performing similar physiological functions throughout the body share similar transcription factor-mediated architectural "blueprints."

journal_name

Genes Dev

journal_title

Genes & development

authors

Lo HG,Jin RU,Sibbel G,Liu D,Karki A,Joens MS,Madison BB,Zhang B,Blanc V,Fitzpatrick JA,Davidson NO,Konieczny SF,Mills JC

doi

10.1101/gad.285684.116

subject

Has Abstract

pub_date

2017-01-15 00:00:00

pages

154-171

issue

2

eissn

0890-9369

issn

1549-5477

pii

gad.285684.116

journal_volume

31

pub_type

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