Epigenetic Regulation of Cell Cycle-Promoting Genes By Ikaros and HDAC1 in Acute Lymphoblastic Leukemia

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3571-3571
Author(s):  
Sunil Muthusami ◽  
Chunhua Song ◽  
Xiaokang Pan ◽  
Chandrika S. Gowda ◽  
Kimberly J Payne ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Chromatin Remodeling ◽  
Transcriptional Repression ◽  
Cell Cycle Progression ◽  
Target Genes ◽  
Lymphoblastic Leukemia ◽  
Promoter Regions ◽  
Cycle Progression ◽  
Repressive Chromatin

Abstract B-cell acute lymphoblastic leukemia (B-ALL) is the most common childhood leukemia. Expression profiling has identified IKZF1 (Ikaros) as a major tumor suppressor in B-ALL and established reduced Ikaros function as a poor prognostic marker for this disease. Ikaros regulates expression of its target genes via chromatin remodeling. In vivo, Ikaros can form a complex with histone deacetylases HDAC1 and/or HDAC2 as well as the NuRD chromatin remodeling complex. The mechanisms by which Ikaros exerts its tumor suppressor function and regulates gene expression in B-ALL are unknown. Here we report the use of chromatin immunoprecipitation coupled with next generation sequencing (ChIP-SEQ) to identify genes that are regulated by Ikaros in vivo and to determine the role of Ikaros in chromatin remodeling in B-ALL. Results reveal that Ikaros binds to the promoter regions of a large number of genes that are critical for cell cycle progression. These include CDC2, CDC16, CDC25A, ANAPC1, and ANAPC7. Overexpression of Ikaros in leukemia cells resulted in transcriptional repression of Ikaros target genes. Results from luciferase reporter assays performed using the respective promoters of Ikaros target genes support a role for Ikaros as a transcriptional repressor of these genes. Downregulation of Ikaros by siRNA resulted in increased expression of Ikaros target genes that control cell cycle progression. These results suggest that Ikaros functions as a negative regulator of cell cycle progression by repressing transcription of cell cycle-promoting genes. Next, we studied how Ikaros binding affects the epigenetic signature at promoters of Ikaros target genes. Global epigenetic mapping showed that Ikaros binding at the promoter region of cell cycle-promoting genes is associated with the formation of one of two types of repressive epigenetic marks – either H3K27me3 or H3K9me3. While these epigenetic marks were mutually exclusive, they were both associated with the loss of H3K9 acetylation and transcriptional repression. Serial qChIP assays spanning promoters of the Ikaros target genes revealed that the presence of H3K27me3 is associated with Ikaros and HDAC1 binding, while the H3K9me3 modification is associated with Ikaros binding and the absence of HDAC1. ChIP-SEQ analysis of HDAC1 global genomic binding demonstrated that over 80% of H3K27me3 modifications at promoter regions are associated with HDAC1 binding at surrounding sites. The treatment of leukemia cells with the histone deacetylase inhibitor – trichostatin (TSA) resulted in a severe reduction of global levels of H3K27me3, as evidenced by Wesern blot. These data suggest that HDAC1 activity in leukemia is essential for the formation of repressive chromatin that is characterized by the presence of H3K27me3. Our data suggest that Ikaros binding at the promoters of its target genes can result in the formation of repressive chromatin by two distinct mechanisms: 1) direct Ikaros binding resulting in increased H3K9me3 or 2) Ikaros recruitment of HDAC1 with increased H3K27me3 modifications. These data suggest distinct mechanisms for the regulation of chromatin remodeling and target gene expression by Ikaros alone, and Ikaros in complex with HDAC1. In conclusion, the presented data suggest that HDAC1 has a key role in regulating cell cycle progression and proliferation in B-ALL. Our results identify novel, Ikaros-mediated mechanisms of epigenetic regulation that contribute to tumor suppression in leukemia. Supported by National Institutes of Health R01 HL095120, and the Four Diamonds Fund Endowment. Disclosures No relevant conflicts of interest to declare.

scholarly journals EGFR-ERK induced activation of GRHL1 promotes cell cycle progression by up-regulating cell cycle related genes in lung cancer

2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Yiming He ◽  
Mingxi Gan ◽  
Yanan Wang ◽  
Tong Huang ◽  
Jianbin Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Potential Role ◽  
Target Genes ◽  
Nuclear Translocation ◽  
Phosphorylation Site ◽  
Promoter Regions ◽  
Cycle Progression

AbstractGrainyhead-like 1 (GRHL1) is a transcription factor involved in embryonic development. However, little is known about the biological functions of GRHL1 in cancer. In this study, we found that GRHL1 was upregulated in non-small cell lung cancer (NSCLC) and correlated with poor survival of patients. GRHL1 overexpression promoted the proliferation of NSCLC cells and knocking down GRHL1 inhibited the proliferation. RNA sequencing showed that a series of cell cycle-related genes were altered when knocking down GRHL1. We further demonstrated that GRHL1 could regulate the expression of cell cycle-related genes by binding to the promoter regions and increasing the transcription of the target genes. Besides, we also found that EGF stimulation could activate GRHL1 and promoted its nuclear translocation. We identified the key phosphorylation site at Ser76 on GRHL1 that is regulated by the EGFR-ERK axis. Taken together, these findings elucidate a new function of GRHL1 on regulating the cell cycle progression and point out the potential role of GRHL1 as a drug target in NSCLC.

scholarly journals Lamina-associated polypeptide 2α regulates cell cycle progression and differentiation via the retinoblastoma–E2F pathway

2006 ◽  
Vol 173 (1) ◽  
pp. 83-93 ◽  
Author(s):  
Daniela Dorner ◽  
Sylvia Vlcek ◽  
Nicole Foeger ◽  
Andreas Gajewski ◽  
Christian Makolm ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Target Genes ◽  
Serum Starvation ◽  
Dependent Manner ◽  
Cycle Progression ◽  
Promoter Sequences ◽  
Delayed Entry ◽  
Accelerated Proliferation

Lamina-associated polypeptide (LAP) 2α is a nonmembrane-bound LAP2 isoform that forms complexes with nucleoplasmic A-type lamins. In this study, we show that the overexpression of LAP2α in fibroblasts reduced proliferation and delayed entry into the cell cycle from a G0 arrest. In contrast, stable down-regulation of LAP2α by RNA interference accelerated proliferation and interfered with cell cycle exit upon serum starvation. The LAP2α-linked cell cycle phenotype is mediated by the retinoblastoma (Rb) protein because the LAP2α COOH terminus directly bound Rb, and overexpressed LAP2α inhibited E2F/Rb-dependent reporter gene activity in G1 phase in an Rb-dependent manner. Furthermore, LAP2α associated with promoter sequences in endogenous E2F/Rb-dependent target genes in vivo and negatively affected their expression. In addition, the expression of LAP2α in proliferating preadipocytes caused the accumulation of hypophosphorylated Rb, which is reminiscent of noncycling cells, and initiated partial differentiation into adipocytes. The effects of LAP2α on cell cycle progression and differentiation may be highly relevant for the cell- and tissue-specific phenotypes observed in laminopathic diseases.

scholarly journals Dp1 Is Largely Dispensable for Embryonic Development

2004 ◽  
Vol 24 (16) ◽  
pp. 7197-7205 ◽  
Author(s):  
Matthew J. Kohn ◽  
Sandra W. Leung ◽  
Vittoria Criniti ◽  
Monica Agromayor ◽  
Lili Yamasaki
Keyword(s):  
Cell Cycle ◽  
Embryonic Development ◽  
Cell Cycle Progression ◽  
Target Genes ◽  
Es Cells ◽  
Embryonic Stem ◽  
Wild Type ◽  
Cycle Progression ◽  
Cell Cycle Genes

ABSTRACT E2F/DP complexes activate or repress the transcription of E2F target genes, depending on the association of a pRB family member, thereby regulating cell cycle progression. Whereas the E2F family consists of seven members, the DP family contains only two (Dp1 and Dp2), Dp1 being the more highly expressed member. In contrast to the inactivation of individual E2F family members, we have recently demonstrated that loss of Dp1 results in embryonic lethality by embryonic day 12.5 (E12.5) due to the failure of extraembryonic lineages to develop and replicate DNA properly. To bypass this placental requirement and search for roles of Dp1 in the embryo proper, we generated Dp1-deficient embryonic stem (ES) cells that carry the ROSA26-LacZ marker and injected them into wild-type blastocysts to construct Dp1-deficient chimeras. Surprisingly, we recovered mid- to late gestational embryos (E12.5 to E17.5), in which the Dp1-deficient ES cells contributed strongly to most chimeric tissues as judged by X-Gal (5-bromo-4-chloro-3-indolyl-β-d-galactopyranoside) staining and Western blotting. Importantly, the abundance of DP2 protein does not increase and the expression of an array of cell cycle genes is virtually unchanged in Dp1-deficient ES cells or chimeric E15.5 tissues with the absence of Dp1. Thus, Dp1 is largely dispensable for embryonic development, despite the absolute extraembryonic requirement for Dp1, which is highly reminiscent of the restricted roles for Rb and cyclins E1/E2 in vivo.

scholarly journals The SIN3/RPD3 Deacetylase Complex Is Essential for G2 Phase Cell Cycle Progression and Regulation of SMRTER Corepressor Levels

2002 ◽  
Vol 22 (14) ◽  
pp. 4965-4976 ◽  
Author(s):  
Lori A. Pile ◽  
Erin M. Schlag ◽  
David A. Wassarman
Keyword(s):  
Cell Cycle ◽  
Transcriptional Repression ◽  
Cell Cycle Progression ◽  
Target Genes ◽  
Phase Delay ◽  
Phase Cell ◽  
Global Changes ◽  
Cycle Progression ◽  
Protein Levels ◽  
Repression Complex

ABSTRACT The SIN3 corepressor and RPD3 histone deacetylase are components of the evolutionarily conserved SIN3/RPD3 transcriptional repression complex. Here we show that the SIN3/RPD3 complex and the corepressor SMRTER are required for Drosophila G2 phase cell cycle progression. Loss of the SIN3, but not the p55, SAP18, or SAP30, component of the SIN3/RPD3 complex by RNA interference (RNAi) causes a cell cycle delay prior to initiation of mitosis. Loss of RPD3 reduces the growth rate of cells but does not cause a distinct cell cycle defect, suggesting that cells are delayed in multiple phases of the cell cycle, including G2. Thus, the role of the SIN3/RPD3 complex in G2 phase progression appears to be independent of p55, SAP18, and SAP30. SMRTER protein levels are reduced in SIN3 and RPD3 RNAi cells, and loss of SMRTER by RNAi is sufficient to cause a G2 phase delay, demonstrating that regulation of SMRTER protein levels by the SIN3/RPD3 complex is a vital component of the transcriptional repression mechanism. Loss of SIN3 does not affect global acetylation of histones H3 and H4, suggesting that the G2 phase delay is due not to global changes in genome integrity but rather to derepression of SIN3 target genes.

The THAP–zinc finger protein THAP1 regulates endothelial cell proliferation through modulation of pRB/E2F cell-cycle target genes

Blood ◽  
2006 ◽  
Vol 109 (2) ◽  
pp. 584-594 ◽  
Author(s):  
Corinne Cayrol ◽  
Chrystelle Lacroix ◽  
Catherine Mathe ◽  
Vincent Ecochard ◽  
Michele Ceribelli ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Large Scale ◽  
Cell Cycle Progression ◽  
Target Genes ◽  
Zinc Finger Protein ◽  
Endothelial Cell Proliferation ◽  
Cycle Progression ◽  
Transcriptional Target

Abstract We recently cloned a novel human nuclear factor (designated THAP1) from postcapillary venule endothelial cells (ECs) that contains a DNA-binding THAP domain, shared with zebrafish E2F6 and several Caenorhabditis elegans proteins interacting genetically with retinoblastoma gene product (pRB). Here, we show that THAP1 is a physiologic regulator of EC proliferation and cell-cycle progression, 2 essential processes for angiogenesis. Retroviral-mediated gene transfer of THAP1 into primary human ECs inhibited proliferation, and large-scale expression profiling with microarrays revealed that THAP1-mediated growth inhibition is due to coordinated repression of pRB/E2F cell-cycle target genes. Silencing of endogenous THAP1 through RNA interference similarly inhibited EC proliferation and G1/S cell-cycle progression, and resulted in down-regulation of several pRB/E2F cell-cycle target genes, including RRM1, a gene required for S-phase DNA synthesis. Chromatin immunoprecipitation assays in proliferating ECs showed that endogenous THAP1 associates in vivo with a consensus THAP1-binding site found in the RRM1 promoter, indicating that RRM1 is a direct transcriptional target of THAP1. The similar phenotypes observed after THAP1 overexpression and silencing suggest that an optimal range of THAP1 expression is essential for EC proliferation. Together, these data provide the first links in mammals among THAP proteins, cell proliferation, and pRB/E2F cell-cycle pathways.

scholarly journals Targeting Casein Kinase II Exerts a Therapeutic Effect in Pediatric High Risk Leukemia Via Inhibition of Cell Cycle Progression and the PI3K Pathway

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4800-4800
Author(s):  
Chandrika S. Gowda ◽  
Chunhua Song ◽  
Yali Ding ◽  
Sunil Muthusami ◽  
Kimberly Payne ◽  
...  
Keyword(s):  
Cell Cycle ◽  
High Risk ◽  
Tumor Suppressor ◽  
Therapeutic Effect ◽  
Cell Cycle Progression ◽  
Target Genes ◽  
Transcriptional Regulator ◽  
Pi3k Pathway ◽  
Cycle Progression

Abstract IKZF1 (Ikaros) encodes a DNA-binding protein that acts as a tumor suppressor in acute lymphoblastic leukemia. Deletion of one Ikaros allele results in the development of high-risk B-cell acute lymphoblastic leukemia (B-ALL) with a high incidence of relapse and poor prognosis. The mechanisms through which Ikaros suppresses leukemogenesis and that regulate Ikaros tumor suppressor activity in leukemia are unknown. Using a systems biology approach, we determined that Ikaros regulates transcription of genes that control two pathways that are crucial in leukemia cell proliferation: 1) cell cycle progression and 2) the phosphatidylinositol 3-kinase (PI3K) pathway. Gain- and loss-of-function experiments demonstrate that Ikaros represses the transcription of genes that promote cell cycle progression and the PI3K pathway and activates transcription of a gene that suppresses the PI3K pathway. We show that in high-risk B-ALL with deletion of one Ikaros allele, the function of Ikaros as a transcriptional regulator is impaired due to reduced DNA-binding affinity for promoters of its target genes. It has been shown that Ikaros DNA-binding affinity is regulated via direct phosphorylation by pro-oncogenic Casein Kinase II (CK2). CK2 is overexpressed in high-risk B-ALL as compared to normal B-cell precursors, which further reduces Ikaros function in high-risk B-ALL. Treatment of primary high-risk B-ALL (with deletion of one Ikaros allele) using the CK2 specific inhibitor, CX-4945, restored Ikaros function as a transcriptional regulator of the genes that regulate cell cycle progression and the PI3K pathway, and was associated with cell cycle arrest and loss of phosphorylation of the AKT kinase - a downstream target of the PI3K pathway. The use of serial quantitative chromatin immunoprecipitation (qChIP) analyses spanning the promoters of Ikaros target genes demonstrated that Ikaros can repress transcription of its target genes by two different mechanisms: 1) via recruitment of histone deacetylase 1 (HDAC1), which is associated with the formation of repressive chromatin characterized by H3K27me3 and loss of H3K9ac; and 2) via an HDAC1-independent mechanism which is associated with the formation of repressive chromatin characterized by H3K9me3, along with the loss of H3K9ac. The therapeutic effect of CK2 inhibition by CX-4945 on high-risk B-ALL was demonstrated in vivo using 4 different xenografts: 3 different high-risk primary pre-B-ALL xenografts and Nalm6 xenografts. Treatment with CX-4945 showed a strong therapeutic effect in all 4 xenografts, as evidence by reduced leukemia cell number in bone marrow and in spleen, along with prolonged survival of all xenografts. Expression analysis of Ikaros target genes that regulate cell cycle progression and the PI3K pathway in leukemia cells treated in vivo with CX-4945 revealed an expression pattern that was highly similar to that observed with Ikaros overexpression. This suggests that CK2 inhibition in vivo exerts its therapeutic effect on high-risk B-ALL via restoration of Ikaros function as transcriptional regulator of genes that promote cell cycle progression and the PI3K pathway. In summary, our results reveal that: 1) Ikaros functions as a tumor suppressor by suppressing cell cycle progression and the PI3K pathway; 2) Ikaros regulates transcription by inducing two distinct epigenetic alterations at promoters of its target genes and 3) CK2 inhibition with CX-4945 restores Ikaros function as a transcriptional regulator in vivo, and has a strong therapeutic effect in primary xenografts of high-risk B-ALL. These results provide support for the use of CK2 inhibitors in clinical trials for high-risk B-ALL. Supported by the National Institutes of Health R01 HL095120, and the Four Diamonds Fund Endowment. Disclosures No relevant conflicts of interest to declare.

scholarly journals Gfi1 upregulates c-Myc expression and promotes c-Myc-driven cell proliferation

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yangyang Zhang ◽  
Fan Dong
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Dna Binding ◽  
Zinc Finger ◽  
Transcriptional Repression ◽  
Cell Cycle Progression ◽  
Target Genes ◽  
Biological Function ◽  
Transcriptional Repressor ◽  
Cycle Progression

Abstract Gfi1 is a zinc-finger transcriptional repressor that plays an important role in hematopoiesis. When aberrantly activated, Gfi1 may function as a weak oncoprotein in the lymphoid system, but collaborates strongly with c-Myc in lymphomagenesis. The mechanism by which Gfi1 collaborates with c-Myc in lymphomagenesis is incompletely understood. We show here that Gfi1 augmented the expression of c-Myc protein in cells transfected with c-Myc expression constructs. The N-terminal SNAG domain and C-terminal ZF domains of Gfi1, but not its transcriptional repression and DNA binding activities, were required for c-Myc upregulation. We further show that Gfi1 overexpression led to reduced polyubiquitination and increased stability of c-Myc protein. Interestingly, the levels of endogenous c-Myc mRNA and protein were augmented upon Gfi1 overexpression, but reduced following Gfi1 knockdown or knockout, which was associated with a decline in the expression of c-Myc-activated target genes. Consistent with its role in the regulation of c-Myc expression, Gfi1 promoted Myc-driven cell cycle progression and proliferation. Together, these data reveal a novel mechanism by which Gfi1 augments the biological function of c-Myc and may have implications for understanding the functional collaboration between Gfi1 and c-Myc in lymphomagenesis.

Targeting of Casein Kinase II (CK2) Enhances Ikaros-Mediated Control of the Cell Cycle Progression in Pre-Clinical Model of Pre-B-ALL.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2431-2431
Author(s):  
Sinsa Dovat ◽  
Chunhua Song ◽  
Kimberly J Payne ◽  
Chandrika S. Gowda
Keyword(s):  
Cell Cycle ◽  
Tumor Suppressor ◽  
Cell Cycle Progression ◽  
Target Genes ◽  
Signal Transduction Pathway ◽  
Preclinical Model ◽  
Suppressor Activity ◽  
Cycle Progression

Abstract Abstract 2431 The Ikaros (IKZF1) gene encodes a DNA-binding zinc finger protein that functions as a tumor suppressor in leukemia. Defects in the Ikaros gene that lead to its decreased activity are associated with the development of B-cell precursor acute lymphoblastic leukemia (pre-B-ALL). However, the mechanisms by which Ikaros exerts its tumor suppressor activity, as well as the mechanisms that control the tumor suppressor function of Ikaros are poorly understood. Here, we report the identification of two novel Ikaros target genes, as well as a signal transduction pathway that regulates the Ikaros-mediated transcriptional control of these genes in pre-B ALL. We also present evidence that targeting the signal transduction pathway which regulates Ikaros transcriptional control is a potent therapeutic tool for treating pre-B ALL. Analysis of the promoter sequences of the CDC7 and the CDK6 genes revealed multiple evolutionarily-conserved Ikaros consensus binding sites. Using qChIP (quantitative chromatin immunoprecipitation assay) we found that Ikaros binds in vivo to the promoters of the CDC7 and CDK6 genes in the human Nalm6 pre-B ALL cell line, and in primary human pre-B ALL cells. This led to the hypothesis that Ikaros regulates transcription of CDC7 and CDK6 - genes whose expression is essential for cell cycle progression and cellular proliferation. The effect of Ikaros on CDC7 and CDK6 expression was studied using a transient co-transfection assay. Luciferase reporter plasmids containing the CDC7 or CDK6 promoter regions were co-transfected with or without Ikaros into 293T cells. Co-transfection of Ikaros led to decreased luciferase activity, suggesting that Ikaros acts as a repressor of the CDC7 and CDK6 upstream regulatory elements. Increased expression of Ikaros via retroviral transduction in Nalm6 cells resulted in decreased transcription of CDC7 and CDK6. Decreased transcription of these genes was associated with increased binding of Ikaros to their promoter regions as measured by qChIP. These results suggest that Ikaros negatively regulates transcription of CDC7 and CDK6, and thus negatively regulates cell cycle progression in pre-B cell leukemia. We have shown previously that phosphorylation of Ikaros by casein kinase II (CK2) inhibits Ikaros' ability to bind DNA and to regulate transcription of its target genes. CK2 activity is elevated in human leukemia. We tested whether the inhibition of CK2 affects the transcription of CDC7 and CDK6 in pre-B ALL in vitro and in vivo. In vitro treatment of Nalm6 pre-B ALL with TBB, a specific CK2 inhibitor, decreased transcription of CDC7 and CDK6 and was associated with increased binding of Ikaros to the promoters of these genes. Using an in vivo preclinical model of pre-B ALL we tested whether targeting of CK2 would affect transcription of CDC7 and CDK6. In vivo treatment of a human-mouse xenograft model of pre-B ALL with a CK2 inhibitor resulted in decreased transcription of CDC7 and CDK6 and strongly increased Ikaros binding to the promoters of these genes. The in vivo targeting of CK2 provided a strong anti-leukemia effect that resulted in the prolonged survival of treated mice as compared to controls. In summary, our results suggest that Ikaros exerts its tumor suppressor activity in pre-B ALL by repressing transcription of cell cycle-promoting genes. Targeting CK2 in vivo enhances Ikaros-mediated repression of cell cycle progression resulting in an anti-leukemia effect. These data demonstrate the efficacy of CK2 targeting as a treatment for pre-B ALL in a preclinical model. These results provide a mechanistic rationale and support for the use of CK2 inhibitors as a targeted treatment of pre-B ALL in early-stage clinical trials. Supported by National Institutes of Health R01 HL095120 and a St. Baldrick's Foundation Career Development Award (to S.D.). Disclosures: No relevant conflicts of interest to declare.

scholarly journals To Divide or Not to Divide? How Deuterium Affects Growth and Division of Chlamydomonas reinhardtii

Biomolecules ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 861
Author(s):  
Veronika Kselíková ◽  
Vilém Zachleder ◽  
Kateřina Bišová
Keyword(s):  
Cell Cycle ◽  
Chlamydomonas Reinhardtii ◽  
Cell Cycle Progression ◽  
Model Organism ◽  
Cycle Progression ◽  
Synchronous Cultures ◽  
Multiple Fission ◽  
First Choice ◽  
High Doses

Extensive in vivo replacement of hydrogen by deuterium, a stable isotope of hydrogen, induces a distinct stress response, reduces cell growth and impairs cell division in various organisms. Microalgae, including Chlamydomonas reinhardtii, a well-established model organism in cell cycle studies, are no exception. Chlamydomonas reinhardtii, a green unicellular alga of the Chlorophyceae class, divides by multiple fission, grows autotrophically and can be synchronized by alternating light/dark regimes; this makes it a model of first choice to discriminate the effect of deuterium on growth and/or division. Here, we investigate the effects of high doses of deuterium on cell cycle progression in C. reinhardtii. Synchronous cultures of C. reinhardtii were cultivated in growth medium containing 70 or 90% D2O. We characterize specific deuterium-induced shifts in attainment of commitment points during growth and/or division of C. reinhardtii, contradicting the role of the “sizer” in regulating the cell cycle. Consequently, impaired cell cycle progression in deuterated cultures causes (over)accumulation of starch and lipids, suggesting a promising potential for microalgae to produce deuterated organic compounds.

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