MKL1-actin pathway restricts chromatin accessibility and prevents mature pluripotency activation

Research output: Contribution to journalArticle

  • External authors:
  • Xiao Hu
  • Zongzhi Z. Liu
  • Xinyue Chen
  • Vincent P. Schulz
  • Abhishek Kumar
  • Amaleah A. Hartman
  • Jason Weinstein
  • Jessica F. Johnston
  • Elisa C. Rodriguez
  • Anna E. Eastman
  • Jijun Cheng
  • Liz Min
  • Mei Zhong
  • Christopher Carroll
  • Patrick G. Gallagher
  • Jun Lu
  • Megan C. King
  • Diane S. Krause
  • Shangqin Guo


Actin cytoskeleton is well-known for providing structural/mechanical support, but whether and how it regulates chromatin and cell fate reprogramming is far less clear. Here, we report that MKL1, the key transcriptional co-activator of many actin cytoskeletal genes, regulates genomic accessibility and cell fate reprogramming. The MKL1-actin pathway weakens during somatic cell reprogramming by pluripotency transcription factors. Cells that reprogram efficiently display low endogenous MKL1 and inhibition of actin polymerization promotes mature pluripotency activation. Sustained MKL1 expression at a level seen in typical fibroblasts yields excessive actin cytoskeleton, decreases nuclear volume and reduces global chromatin accessibility, stalling cells on their trajectory toward mature pluripotency. In addition, the MKL1-actin imposed block of pluripotency can be bypassed, at least partially, when the Sun2-containing linker of the nucleoskeleton and cytoskeleton (LINC) complex is inhibited. Thus, we unveil a previously unappreciated aspect of control on chromatin and cell fate reprogramming exerted by the MKL1-actin pathway.

Bibliographical metadata

Original languageEnglish
Article number1695
JournalNature Communications
Issue number1
Early online date12 Apr 2019
Publication statusE-pub ahead of print - 12 Apr 2019