A MTA2-SATB2 chromatin complex restrains colonic plasticity toward small intestine by retaining HNF4A at colonic chromatin

A MTA2-SATB2 chromatin complex restrains colonic plasticity toward small intestine by retaining HNF4A at colonic chromatin

Blog Article

Abstract Plasticity among cell lineages is a fundamental, but poorly understood, property of regenerative tissues.In the gut tube, the small intestine absorbs nutrients, whereas the colon Vacuum Cleaners absorbs electrolytes.In a striking display of inherent plasticity, adult colonic mucosa lacking the chromatin factor SATB2 is converted to small intestine.Using proteomics and CRISPR-Cas9 screening, we identify MTA2 as a crucial component of the molecular machinery that, together with SATB2, restrains colonic plasticity.

MTA2 loss in the adult mouse colon activated lipid absorptive genes and functional lipid uptake.Mechanistically, MTA2 co-occupies DNA with HNF4A, an activating pan-intestinal transcription factor (TF), on colonic chromatin.MTA2 loss leads to HNF4A release from colonic chromatin, and accumulation on small intestinal chromatin.SATB2 similarly restrains colonic plasticity through an HNF4A-dependent mechanism.

Our study provides a Plaid Bow generalizable model of lineage plasticity in which broadly-expressed TFs are retained on tissue-specific enhancers to maintain cell identity and prevent activation of alternative lineages, and their release unleashes plasticity.