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

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, Martin Schwartz, Megan C. King, Diane S. Krause and Shangqin Guo ()
Additional contact information
Xiao Hu: Yale University
Zongzhi Z. Liu: Yale University
Xinyue Chen: Yale University
Vincent P. Schulz: Yale University
Abhishek Kumar: Yale University
Amaleah A. Hartman: Yale University
Jason Weinstein: Yale University
Jessica F. Johnston: Yale University
Elisa C. Rodriguez: Yale University
Anna E. Eastman: Yale University
Jijun Cheng: Yale University
Liz Min: Yale University
Mei Zhong: Yale University
Christopher Carroll: Yale University
Patrick G. Gallagher: Yale University
Jun Lu: Yale University
Martin Schwartz: Yale University
Megan C. King: Yale University
Diane S. Krause: Yale University
Shangqin Guo: Yale University

Nature Communications, 2019, vol. 10, issue 1, 1-13

Abstract: Abstract 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.

Date: 2019
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-019-09636-6 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09636-6

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-019-09636-6

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().