Table 1.

c-Kit dysfunction regulates cell-cycle gene expression in cardiomyocytes from hypertensive mice [11]

Gene	x-fold increasea (W/Wv-SAC/WT-SAC) (n = 5–7/group)	Comment
G1/S phase transition and DNA replication
Thymidine kinase 1 (TK1)	2.6b	TK1 regulation (upregulated during S and M phases) provides the pool of dTTP for DNA synthesis in the cell cycle
Ribonucleotide reductase M2 (Rrm2)	2.4b	Rrm2 converts ribonucleoside diphosphates to deoxyribonucleoside diphosphates, which are essential for DNA synthesis
E2F transcription factor 1 (E2f1)	1.7b	E2f1, a key target of the retinoblastoma protein, activates cell cycle progression, but also apoptosis
E2F transcription factor 2 (E2f2)	2.6b	E2f2, a key target of the retinoblastoma protein, induces DNA synthesis in cardiomyocytes but without activation of apoptosis
Cytoskeleton-associated protein 2 (ckap2)	3.3c	Ckap2 is a microtubule component. It is involved in apoptosis, ploidy, and cell cycle progression
DBF4 homolog (DBF4)	(2.5b)	DDK, composed of the catalytic subunit Cdc7 and the regulatory subunit Dbf4, promotes timely S phase progression
Chromatin assembly factor 1, subunit B (Chaf1b)	(3.8b)	Chromatin assembly factor 1 is required for the assembly of histone octamers onto newly replicated DNA
Chromosome transmission fidelity factor 18 (Chtf18)	(4.3b)	Chtf18 is required for sister chromatid cohesion in S phase that is a critical step in high-fidelity cell division
Histone 1h2af (Hist1h2af)	2.9b	Hist1h2af is involved in chromosome organization, biogenesis, and nucleosome assembly
Histone 1h2an (Hist1h2an)	2.8b	Hist1h2an is involved in chromosome organization, biogenesis, and nucleosome assembly
G2/M phase regulation
Cyclin B1 (Ccnb1)	2.6b	The G2 to M phase transition is triggered by the dimerization of cyclin B/cdc2, which are subunits of mitosis-promoting factor
Cell division cycle 25 homolog C (cdc25c)	2.8d	Cyclin B/cdc2 is activated by the phosphatase Cdc25
Cell division cycle 2 homolog A (cdc2)	3.1c	Cdc2, a Ser/Thr kinase, is essential for G1/S and G2/M phase cell cycle transitions
Cell division cycle 20 homolog (cdc20)	(3.0b)	Cdc20 activates anaphase-promoting complex/cyclosome from mitosis through the metaphase-anaphase transition
Forkhead box M1 (Foxm1)	(3.9b)	Foxm1 regulates transcription of proteins involved in G1/S and G2/M phase transitions
Cell division cycle–associated 5 (cdca5)	(2.2b)	Cdca5, a nuclear protein associated with cohesin complex, is involved in chromatin binding and G1/S phase transition
Topoisomerase (DNA) 2 alpha (Top2a)	3.2b	Top2a catalyzes topologic genomic changes needed for chromosome segregation and DNA replication
Thymidylate synthase (Tyms)	1.5b	Tyms is essential for DNA synthesis and repair. Tyms is regulated by E2F-1 and thus is linked to the cell cycle pathway
Cell division cycle–associated 7-like (cdca7 l)	2.1b	Cdca7 l interacts with c-myc and leads to cell proliferation
Sister chromatid separation, kinetocore, and centrosome associated protein
Aurora kinase A (Aurka)	2.6b	Aurora-A and Plk1, which localize aurora-A to centrosomes, are involved in centrosome maturation and spindle assembly
Kinetochore associated 1 (Kntc1)	3.2b	Kntc1 plays important roles in ensuring proper chromosome segregation during cell division
Budding uninhibited by benzimidazoles 1β (Bub1b)	(4.7b)	The Bub1b gene encodes BubR1. BubR1 regulates spindle checkpoint
Centromere protein E (CenpE)	3.3c	CenpE is needed for organization of stable microtubule–kinetochore assembly for proper chromosome segregation in mitosis
Centromere protein M (CenpM)	3.4b	CenpM is required for proper assembly of the CenpA nucleosome–associated complex
Actin and microtubules assembly
Anillin (Anln)	3.1b	Anillin, a cross-linker, binds to filaments in the contractile ring that constricts to form a cleavage furrow during cytokinesis
Diaphanous homolog 3 (Drosophila) (Diap3)	3.5c	Diap3 recruits profilin to the membrane, where it promotes actin polymerization. It is required for cytokinesis
Central spindle and aurora kinase complex/microtubule–associated protein
Protein-regulating cytokinesis 1 (Prc1)	3.5b	Microtubule-associated Prc1 is an anaphase-specific binding partner for Plk1. This interaction is required for cytokinesis
Kinesin family member 22 (Kif22)	2.7c	Kif22, a microtubule-dependent molecular motor, is essential for metaphase chromosome alignment and maintenance
Kinesin family member 4 (Kif4)	2.9b	Kif4 is a microtubule-based motor protein that plays a crucial role in cell division
Kinesin family member C5A (Kifc1)	2.5c	Kifc1 is a minus-end-directed microtubule-dependent motor involved in the control of centrosome duplication
Kinesin family member 2C (Kif2c)	(3.6b)	Kif2c, a microtubule-dependent molecular motor, is important for anaphase chromosome segregation
Aurora kinase B (Aurkb)	2.6b	Aurora B phosphorylates the microtubule-binding proteins, which leads to detachment of microtubules from kinetochores
Inner centromere protein (Incenp)	3.0c	Incenp, which activates aurora-B kinase, complexes with survivin to attach chromosomes correctly to spindle microtubules
Survivin (Birc5)	2.9c	Survivin, a subunit of the chromosomal passenger complex, is essential for proper chromosome segregation and cytokinesis
Polo-like kinase 1 (Drosophila) (Plk1)	2.4b	Plk1 plays a critical role in centrosome maturation, mitotic spindle assembly, mitotic entry and exit, and cytokinesis
Nucleolar and spindle–associated protein 1 (Nusap1)	3.2b	NuSAP is an essential microtubule-stabilizing and -bundling protein enriched at the central part of the spindle.
Meiosis-specific nuclear structural protein 1 (Mns1)	2.3b	MNS1 maintains appropriate nuclear morphology during meiotic prophase
Claspin (Clspn)	2.9c	Plk1 phosphorylates claspin, releasing it from DNA, thereby contributing to Chk1 (a cell cycle checkpoint) inactivation

SAC suprarenal aortic constriction, WT wild type, dTTP deoxythymidine triphosphate thymidine 5′-triphosphate, DDK DBF4 dependent kinase

^amRNA transcript levels normalized to glyceraldehyde phosphate dehydrogenase (GAPDH) mRNA, were determined using q-reverse transcriptase-polymerase chain reaction (RT-PCR). Values are x-fold increases in the normalized mRNA expression level in W/W^v 7-day SAC cardiomyocytes relative to that in WT 7-day SAC cardiomyocytes. Values in parentheses are the x-fold changes determined by microarray analyses

^bp<0.05

^cp<0.01

^dp<0.001, Student's t test