Klf1, a C2H2 Zinc Finger-Transcription Factor, Is Required for Cell Wall Maintenance during Long-Term Quiescence in Differentiated G0 Phase

Abstract

Fission yeast, Schizoaccharomyces pombe, is a model for studying cellular quiescence. Shifting to a medium that lacks a nitrogen-source induces proliferative cells to enter long-term G0 quiescence. Klf1 is a Krüppel-like transcription factor with a 7-amino acid Cys2His2-type zinc finger motif. The deletion mutant, ∆klf1, normally divides in vegetative medium, but proliferation is not restored after long-term G0 quiescence. Cell biologic, transcriptomic, and metabolomic analyses revealed a unique phenotype of the ∆klf1 mutant in quiescence. Mutant cells had diminished transcripts related to signaling molecules for switching to differentiation; however, proliferative metabolites for cell-wall assembly and antioxidants had significantly increased. Further, the size of ∆klf1 cells increased markedly during quiescence due to the aberrant accumulation of Calcofluor-positive, chitin-like materials beneath the cell wall. After 4 weeks of quiescence, reversible proliferation ability was lost, but metabolism was maintained. Klf1 thus plays a role in G0 phase longevity by enhancing the differentiation signal and suppressing metabolism for growth. If Klf1 is lost, S. pombe fails to maintain a constant cell size and normal cell morphology during quiescence.

The GATA transcription factor Gaf1 represses tRNA genes, inhibits growth, and extends chronological lifespan downstream of fission yeast TORC1

“…Typically, these factors were induced in wild-type cells after TORC1 inhibition, but less so in gaf1Δ cells. Many of these factors are involved in different stress responses or cell-cycle regulation, including Atf1 (Wilkinson et al, 1996), Cbf12 (Chen et al, 2003), Fep1 (Bekker et al, 1991), Fil1 (Duncan et al, 2018), Hsr1 (Chen et al, 2008), Klf1 (Shimanuki et al, 2013), Loz1 (Corkins et al, 2013), Pap1 (Chen et al, 2008), Php3 (Mercier et al, 2006) and Sep1 (Rustici et al, 2004). The large number of transcription-factor targets indicates that Gaf1 may indirectly control some Gaf1-dependent genes by regulating other transcription factors.…”

Unexpected similarities between theSchizosaccharomycesand human blood metabolomes, and novel human metabolites

“…32 Also we made targeted measurements of intermediates of the coenzyme A biosynthetic pathway from pantothenate, 33 investigated changes in the cellular metabolome upon glucose 34 and nitrogen starvation, 35 and accumulation of various metabolites in the quiescence-defective Dklf1 mutant. 36 These studies showed that S. pombe may be used as a model organism to study comprehensive metabolic patterns under defined genetic and physiological conditions. S. pombe cells grow and divide in culture media containing only 0.08% glucose as rapidly as in regular synthetic culture media containing 2% glucose; however, their division rate is impaired if extracellular glucose drops below 0.08% 34 (4.4 mM), a concentration that is roughly equivalent to that in the blood of healthy humans before breakfast.…”

Myocardial ischemic preconditioning upregulated protein 1(Mipu1):zinc finger protein 667 - a multifunctional KRAB/C2H2 zinc finger protein

“…The zinc finger proteins that contain KRAB, also called KRAB zinc finger proteins (KRAB-containing zinc finger proteins, KZNF), make up almost one-third (290 kinds) of all zinc finger proteins (799 kinds). They are the largest transcription repressor family in mammals and play an important role in embryonic development, cell differentiation, cell transformation, and cell cycle regulation ( 14 - 18 ) ( Table 1 ; 19-27).…”