Cell Stem Cell - Klf4 Organizes Long-Range Chromosomal Interactions with the Oct4 Locus in Reprogramming and Pluripotency

Epigenetic mechanisms underlying somatic reprogramming have been extensively studied, but little is known about the nuclear architecture of pluripotent stem cells (PSCs). Using circular chromosome conformation capture with high-throughput sequencing (4C-seq) and fluorescence in situ hybridization (FISH), we identified chromosomal regions that colocalize frequently with the Oct4 locus in PSCs. These PSC-specific long-range interactions are established prior to transcriptional activation of endogenous Oct4 during reprogramming to induced PSCs and are facilitated by Klf4-mediated recruitment of cohesin. Depletion of Klf4 leads to unloading of cohesin at the Oct4 enhancer and disrupts long-range interactions prior to loss of Oct4 transcription and subsequent PSC differentiation, suggesting a causative role for Klf4 in facilitating long-range interactions independent of its transcriptional activity. Taken together, our results delineate the basic nuclear organization at the Oct4 locus in PSCs and suggest a functional role for Klf4-mediated higher-order chromatin structure in maintaining and inducing pluripotency.

KEYWORDS

SHARE & LIKE

COMMENTS

ABOUT THE AUTHOR

干细胞-细胞(CELL STEM CELL)

0 Following 0 Fans 0 Projects 24 Articles

SIMILAR ARTICLES

Shwachman-Diamond syndrome (SDS), a rare autosomal-recessive disorder characterized by exocrine pancreatic insufficiency and hematopoietic dysfunction,

Read More

Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disease, characterized by motor neuron (MN) death, for which there are n

Read More

p53 is a transcription factor that mediates tumor suppressor responses. Correct folding of the p53 protein is essential for these activities, and point

Read More

Shwachman-Diamond syndrome (SDS), a rare autosomal-recessive disorder characterized by exocrine pancreatic insufficiency and hematopoietic dysfunction,

Read More

The bone marrow (BM) niche comprises multiple cell types that regulate hematopoietic stem/progenitor cell (HSPC) migration out of the niche and into th

Read More

Understanding the fetal hepatic niche is essential for optimizing the generation of functional hepatocyte-like cells (hepatic cells) from human embryon

Read More

The Adenomatous Polyposis Coli (APC) gene is mutated in the majority of colorectal cancers (CRCs). Loss of APC leads to constitutively active WNT signa

Read More

Reactive oxygen species (ROS) generation is implicated in stem cell self-renewal in several tissues but is thought to be detrimental for spermatogenesi

Read More

Huntington’s disease (HD) is a neurodegenerative disease characterized in part by the loss of striatopallidal medium spiny projection neurons (MSNs). E

Read More

The chromatin state of pluripotency genes has been studied extensively in embryonic stem cells (ESCs) and differentiated cells, but their potential int

Read More