Low complexity domains, condensates, and stem cell pluripotency

Abstract

Biological reactions require self-assembly of factors in the complex cellular milieu. Recent evidence indicates that intrinsically disordered, low-complexity sequence domains (LCDs) found in regulatory factors mediate diverse cellular processes from gene expression to DNA repair to signal transduction, by enriching specific biomolecules in membraneless compartments or hubs that may undergo liquid-liquid phase separation (LLPS). In this review, we discuss how embryonic stem cells take advantage of LCD-driven interactions to promote cell-specific transcription, DNA damage response, and DNA repair. We propose that LCD-mediated interactions play key roles in stem cell maintenance and safeguarding genome integrity.

ATP-binding cassette protein ABCF1 couples transcription and genome surveillance in embryonic stem cells through low-complexity domain

“…S3A) and consistent with one of the largest classes of intrinsically disordered region called polyampholytes ( 29 ). These clusters of positively and negatively charged amino acid, interspersed with hydrophobic residues such as phenylalanine, are known to promote LLPS ( 30 , 31 ). Given the recent appreciation that the ability of LCDs in transcription factors and coactivators to form LLPS droplets in vitro often correlates with their transactivation activities ( 7 – 9 , 32 ), we next investigated whether ABCF1 proteins are also capable of forming liquid droplets in vitro and in cells.…”

The Role of ATP-Binding Cassette Proteins in Stem Cell Pluripotency

“…Whether or not ABCF1 also recognizes intracellular DNAs in PSCs and the biological consequences is unknown. Our recent work indicates that PSCs co-opt ABCF1 s ability to detect intracellular DNAs to modulate stem cell-specific transcription in response to genome instability (discussed in the next sections) [48,133].…”

Phase separation of BuGZ regulates gut regeneration and aging through interaction with m6A regulators

“…Biological functions and impacts of phase separation have been ill-defined and fueled by the ease of visualizing the droplet-shaped coacervations and disrupting the reversible condensate assembly in vivo and in vitro, which have advanced various biological fields 2 , 8 – 10 . Most studies on phase separation referred to stem cells focus on embryonic stem cells (ESCs) during organ development instead of adult stem cells (ASCs, also known as resident stem cells) 11 , 12 during tissue homeostasis and aging. A recent finding revealing that phase separation regulates the asymmetric localization of Numb and PAR complexes and contributes to neuroblast division in neural stem cells (NSC), suggests a possible regulatory role of LLPS on some ASCs 13 , 14 .…”