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Biomedical subjects

A Giordano

Publications and source records attributed to A Giordano.

At least 19 recordsLinked to original sources
PubMed1996

Decorin-induced growth suppression is associated with up-regulation of p21, an inhibitor of cyclin-dependent kinases.

The secreted proteoglycan decorin has been implicated in the negative control of cell proliferation primarily by virtue of its ability to block transforming growth factor-beta. Moreover, decorin expression is markedly up-regulated during quiescence but suppressed upon viral transformation, whereas de novo decorin expression in colon carcinoma cells abrogates the malignant phenotype by arresting the cells in the G1 phase of the cell cycle. Here we show that this decorin-induced growth arrest is associated with up-regulation of p21 mRNA and protein in a transforming growth factor-beta- and p53-independent pathway. The augmented p21 protein is present as a multimeric complex with various cyclins and cyclin-dependent kinases in the nuclei of decorin-expressing cells, thereby leading to suppression of cyclin-dependent kinase activity and block of cell division. Through the usage of decorin-specific antisense oligodeoxynucleotide treatment, we demonstrate that the expression of decorin is closely linked to that of p21 and that abrogation of decorin leads to suppression of p21 and restoration of cell division. Collectively, our results provide a plausible mechanism by which decorin may contribute to retard and suppress the growth of tumor cells in vivo.

Base Sequence↗
PubMed1996

Detection and significance of a discrete very low frequency rhythm in RR interval variability in chronic congestive heart failure.

Although in advanced chronic congestive heart failure (CHF) very low frequency (< 0.04 Hz, VLF) oscillations are prominent, the clinical importance and the physiologic basis of these rhythms have not been elucidated. To investigate the physiologic determinants of the VLF rhythms in RR interval variability, we studied 36 patients with stable, moderate to severe CHF (33 men, age: 58 +/- 8 years, ejection fraction 25 +/- 10%, peak oxygen consumption 18.1 +/- 4.6 ml/kg/min) and 12 age- and sex-matched controls using autoregressive spectral analysis of RR interval, blood pressure, and respiratory signals during controlled conditions. We quantified low frequency (LF) (0.04 to 0.15 Hz), high frequency (HF) (0.15 to 0.40 Hz), VLF, and total power (0 to 0.5 Hz), and calculated the coherence between systolic blood pressure and RR interval variability within each band. Peripheral chemosensitivity was assessed by the ventilatory response to hypoxia using transient inhalation of pure nitrogen. The influence of transient inactivation of peripheral chemoreceptors on the VLF rhythm was investigated by exposing 6 patients to hyperoxic (60% oxygen) conditions for 20 minutes. Twenty-three patients (64%) with CHF, but no controls, had a discrete VLF rhythm (0.019 +/- 0.008 Hz) in RR variability. The presence of VLF rhythm was not related to any difference in clinical parameters (etiology, New York Heart Association class, ejection fraction, oxygen uptake) but rather to a different pattern in RR interval and blood pressure variability: lower LF power (2.8 +/- 1.6 ms2 natural logarithm [ln]) compared either to patients without VLF (4.0 +/- 1.3 ms2 ln) or to controls (5.9 +/- 0.7 ms2 ln), higher percentage of power within VLF band (86.3 +/- 8.3% vs 77.5 +/- 7.9% and 61.5 +/- 14.1%) and a markedly impaired coherence between RR interval and systolic blood pressure variability within the LF band (0.26 +/- 0.10 vs 0.42 +/- 0.18 and 0.63 +/- 0.15, in patients with vs without VLF peak and controls, respectively). Patients with VLF had significantly increased hypoxic chemosensitivity, and hyperoxic conditions were able to decrease VLF power and abolish the VLF rhythm in 5 of 6 patients with CHF. Discrete VLF oscillations in RR variability are common in patients with advanced CHF and appear to be related to severely impaired autonomic regulation and suppression of baroreceptor function, with enhancement of hypoxic chemosensitivity. We hypothesize that this rhythm represents an enhanced chemoreflex harmonic oscillation in CHF patients, which may have application for arrhythmogenesis.

Autonomic Nervous System↗
PubMed1996

Myocardial Infarction Is Coupled with the Activation of Cyclins and Cyclin-Dependent Kinases in Myocytes

To determine whether the molecular components implicated in the regulation of the cell cycle are activated in myocytes after infarction, the expression of cyclins E, A, and B and the levels of their associated kinase activity were measured at 1 and 7 days following surgery. The quantity of cdk2 and cdc2 and the level of their kinase activity were also determined. Myocardial infarction was characterized by an increase in cyclins E, A, and B and cdc2 proteins in the surviving myocytes at 1 and 7 days. Cyclin E, A, and B and cdk2 and cdc2 kinase activity also increased. The quantity of cyclins E and A and the level of cyclin E-associated kinase activity in myocytes after infarction were comparable with those measured in neonatal myocytes. Moreover, cdc2 protein and cdc2 kinase activity in myocytes reached levels after infarction which were similar to those in neonatal myocytes. Thus, myocytes react to myocardial infarction by activating cyclins and cyclin-dependent kinases which may be coupled with the regeneration of muscle mass and recovery of ventricular function.

Journal Article↗
PubMed1996

Genomic structure of the human retinoblastoma-related Rb2/p130 gene.

The human Rb2/p130 gene shares many structural and functional features with the retinoblastoma gene and the retinoblastoma-related p107 gene. In the present study, we have cloned and partially sequenced the gene coding for the Rb2/p130 protein from human genomic libraries. The complete intron-exon organization of this gene has been elucidated. The gene contains 22 exons spanning over 50 kb of genomic DNA. The length of individual exons ranges from 65 to 1517 bp. The largest intron spans over 9 kb, and the smallest has only 82 bp. The 5' flanking region revealed a structural organization characteristic of promoters of "housekeeping" and growth control-related genes. A typical TATA or CAAT box is not present, but there are several GC boxes and potential binding sites for numerous transcription factors. This study provides the molecular basis for understanding the transcriptional control of the Rb2/p130 gene and for implementing a comprehensive Rb2/p130 mutation screen using genomic DNA as a template.

Amino Acid Sequence↗
PubMed1996

Functional analysis of pRb2/p130 interaction with cyclins.

The retinoblastoma (Rb) family consists of the tumor suppressor pRb and related proteins p107 and pRb2/p130. Ectopic expression of pRb and p107 results in a growth arrest of sensitive cells in the G1 phase of the cell cycle. We demonstrated here that the growth-suppressive properties of pRb2/p130 were also specific for the G1 phase. The A-, E-, and D-type cyclins as well as transcription factor E2F1 and the E1A viral oncoprotein were able to rescue the pRb2/p130-mediated G1 growth arrest in SAOS-2 cells. The rescue with cyclins A and E correlated with their physical interaction with pRb2/p130, which surprisingly has been found to occur over all phases of the cell cycle. The phosphorylation status as well as the kinase activity associated with pRb2/p130 dramatically increased near the G1-S-phase transition. This suggests that, like the other Rb family members, pRb and p107, the phosphorylation of pRb2/p130 is controlled by the cell cycle machinery and that pRb2/p130 may indeed be another key G1-S-phase regulator.

CDC2-CDC28 Kinases↗
PubMed1996

Human p300 protein is a coactivator for the transcription factor MyoD.

Human p300 protein is a cellular target of adenoviral E1A oncoprotein and a potential transcriptional coactivator. Both p300 and Rb family protein-binding regions of E1A are required for the repression of muscle gene expression, which is regulated by MyoD family transactivators. This implies that p300 is involved in MyoD-dependent transactivation. We show that the repression of MyoD-mediated E box (MyoD consensus) reporter activity by E1A is correlated with its interaction with p300, indicating that p300 participates in MyoD-dependent transactivation. In addition, p300 is able to interact both in vivo and in vitro with MyoD through a portion at the carboxyl-terminal cysteine/histidine-rich domain and associates with the components of the basal transcriptional complex through its two separate transactivation domains at the amino and carboxyl termini. Consistent with its role as a coactivator, p300 potentiates MyoD-activated transcription.

Cysteine↗
PubMed1996

A preliminary study of growth hormone in the treatment of dilated cardiomyopathy.

BACKGROUND: Cardiac hypertrophy is a physiologic response that allows the heart to adapt to an excess hemodynamic load. We hypothesized that inducing cardiac hypertrophy with recombinant human growth hormone might be an effective approach to the treatment of idiopathic dilated cardiomyopathy, a condition in which compensatory cardiac hypertrophy is believed to be deficient. METHODS: Seven patients with idiopathic dilated cardiomyopathy and moderate-to-severe heart failure were studied at base line, after three months of therapy with human growth hormone, and three months after the discontinuation of growth hormone. Standard therapy for heart failure was continued throughout the study. Cardiac function was evaluated with Doppler echocardiography, right-heart catheterization, and exercise testing. RESULTS: When administered at a dose of 14 IU per week, growth hormone doubled the serum concentrations of insulin-like growth factor I. Growth hormone increased left-ventricular-wall thickness and reduced chamber size significantly. Consequently, end-systolic wall stress (a function of both wall thickness and chamber size) fell markedly (from a mean [+/-SE] of 144+/-11 to 85+/-8 dyn per square centimeter, P<0.001). Growth hormone improved cardiac output, particularly during exercise (from 7.4+/-0.7 to 9.7+/-0.9 liters per minute, P=0.003), and enhanced ventricular work, despite reductions in myocardial oxygen consumption (from 56+/-6 to 39+/-5 ml per minute, P=0.005) and energy production (from 1014+/-100 to 701+/-80 J per minute, P=0.002). Thus, ventricular mechanical efficiency rose from 9+/-2 to 21+/-5 percent (P=0.006). Growth hormone also improved clinical symptoms, exercise capacity, and the patients' quality of life. The changes in cardiac size and shape, systolic function, and exercise tolerance were partially reversed three months after growth hormone was discontinued. CONCLUSIONS: Recombinant human growth hormone administered for three months to patients with idiopathic dilated cardiomyopathy increased myocardial mass and reduced the size of the left ventricular chamber, resulting in improvement in hemodynamics, myocardial energy metabolism, and clinical status.

Adult↗
PubMed1996

Different effect of height on latency of leg and foot short- and medium- latency EMG responses to perturbation of stance in humans.

In standing humans, platform perturbations evoked short- (SLR) and medium-latency responses (MLR) in soleus (Sol), tibialis anterior (TA) and flexor digitorum brevis (FDB) muscles. The latency of all responses significantly increased with subjects' height. The slope of the regression lines for the MLRs versus height was significantly steeper than that for the SLRs. The conduction velocity of the afferent fibres mediating the FDB MLR, calculated on the basis of the regression, was 17.5 m/s. These findings indicate that the MLRs are transmitted through afferent fibres slower than those mediating the SLRs. While the latter fibres are spindle group Ia afferents, the former are suggested to be group II fibres.

Adolescent↗
PubMed1996

Tyrosine hydroxylase, neuropeptide Y, substance P, calcitonin gene-related peptide and vasoactive intestinal peptide in nerves of rat periovarian adipose tissue: an immunohistochemical and ultrastructural investigation.

Rat periovarian adipose tissue contains unilocular adipocytes and some multilocular adipocytes that, following acclimation to cold, become more numerous and give rise to periovarian brown fat areas. We studied the occurrence and distribution of tyrosine hydroxylase, neuropeptide Y, substance P, calcitonin gene-related peptide, vasoactive intestinal peptide, methionine enkephalin, neurotensin, galanin, and cholecystokinin 9-20 in the nerves of rat periovarian tissue maintained at 20 degrees C (control rats), acclimated at 4 degrees C (cold acclimated rats) and at 28 degrees C (warm-acclimated rats). In the periovarian tissue of control and warm-acclimated rats, tyrosine hydroxylase-like, neuropeptide Y-like, substance P-like and calcitonin gene-related peptide-like immunoreactive elements (putative nerves) were present in the blood vessels. In the periovarian tissue of cold-acclimated rats, we found: (1) a more widespread vascular distribution of these neuropeptides; (2) tyrosine hydroxylase-like and calcitonin gene-related peptide-like immunoreactive elements among paucilocular and multilocular adipocytes (parenchymal-like nerves); (3) vasoactive intestinal peptide-like immunoreactive elements in some arteries. Investigation by EM showed the presence of heterogeneous non-myelinated axons both associated with capillaries and among paucilocular and multilocular adipocytes (parenchymal fibres) in periovarian brown fat areas. In conclusion, periovarian brown fat contains the same neuropeptides, with the same vascular and parenchymal distribution, already seen in typical depots of brown fat.

Adipose Tissue, Brown↗
PubMed1996

Expanding concepts in ischaemic heart disease: implications for clinical practice and research.

In the late Eighties, a series of observations from several institutions around the world has dramatically revolutionized the traditional notion that the occurrence of myocardial infarction was related most of the time to the development of critical flow-limiting coronary stenosis. All these studies showed that the infarct-related artery had only minimal or mild stenosis in about two thirds of the cases. Therefore, contrary to our previous beliefs, in clinical practice the detection of coronary stenosis has a lesser role in the prognostic assessment of patients with ischaemic heart disease, unless associated with extensive ischemia or with phases of instability. In fact, the major determinants of prognosis are represented by age, left ventricular function, effort tolerance and especially by the clinical stability or instability of angina. According to the Bayesian an theorem, in low risk patients any diagnostic test has a very low predictive accuracy, unless very high specificity criteria are used. The value of diagnostic tests in the assessment of patients' prognosis should be evaluated in intermediate risk groups. The emphasis of clinical research has, therefore, shifted from the detection of flow-limiting stenosis to the study of the multiple and varied dynamic causes of stable and unstable ischaemia, where the possibilities of making new, seminal observations are greater.

Aged↗
PubMed1995

Expression of cell cycle regulatory factors in differentiating osteoblasts: postproliferative up-regulation of cyclins B and E.

The representation of cyclins and cyclin-dependent kinases (cdks) was analyzed during progressive development of the bone cell phenotype in cultures of normal diploid rat calvarial osteoblasts. Three developmental stages were examined: (a) proliferation; (b) monolayer confluency; and (c) mineralization of the bone extracellular matrix. We demonstrate that the presence of cyclins and cdks is not restricted to the proliferation period. Consistent with their role in cell cycle progression, cdc2 and cdk2 decrease postproliferatively. However, cdk4 and cyclins A, B, and D1 persist in confluent cells. Cyclin E is significantly up-regulated during the extracellular matrix mineralization developmental period. Examination of the cytoplasmic levels of these cell cycle regulatory proteins indicates a marked increase in cyclin B in the late differentiation stage. The elevation of nuclear cyclin E and cytoplasmic cyclin B is not observed in osteoblasts maintained under culture conditions that do not support differentiation. Furthermore, treatment with transforming growth factor beta for 48 h during the proliferation period renders the cells incompetent for differentiation and abrogates the postproliferative up-regulation of cyclins B and E. Density-induced growth inhibition of ROS 17/2.8 osteosarcoma cells is not accompanied by up-regulation of nuclear cyclin E and cytoplasmic cyclin B when compared to the proliferation period. This observation is consistent with abrogation of both growth control and differentiation regulatory mechanisms in tumor cells. These results suggest that cell cycle regulatory proteins function not only during proliferation but may also play a role in normal diploid osteoblast differentiation.

Animals↗
PubMed1995

The cdc-2-related kinase, PISSLRE, is essential for cell growth and acts in G2 phase of the cell cycle.

Mammalian cell cycle progression is regulated by several protein kinases that are activated by cyclically expressed proteins called cyclins. These cyclin-dependent kinases, the prototype of which is the cdc2 mitosis-promoting kinase, are known to phosphorylate substrates the modified status of which is critical for the cell to progress into sequential phases of the cycle. Recently, a new cdc2-related protein kinase has been discovered. PISSLRE, named with respect to its homology to the cdc2 PSTAIRE amino acid domain. Here we report that by using both antisense and dominant-negative mutant constructs of PISSLRE when overexpressed in U2OS cells, a growth suppression is found. Furthermore, the dominant negative forms of PISSLRE halt cell cycle progression in G2-M. Therefore, PISSLRE is essential for cellular proliferation, and its effect is exerted in G2-M. This describes the first evidence since cdc2 of a cdc2-related kinase acting through G2-M.

Amino Acid Sequence↗
PubMed1995

Prognostic significance of maximal exercise testing after myocardial infarction treated with thrombolytic agents: the GISSI-2 data-base. Gruppo Italiano per lo Studio della Sopravvivenza Nell'Infarto.

Exercise testing helped in diagnosing postinfarction patients in the prethrombolytic era. Over the past decade acute myocardial infarction treatment has changed because of new thrombolytic therapies and consequently, the value of exercise testing is under debate. The GISSI-2 database allowed us to reevaluate the prognostic role of exercise testing in thrombolysed patients. The exercise test was performed in 6296 patients, on average 28 days after randomisation. The test was not performed in 3923 patients because of contraindications. The test was judged positive for residual ischaemia in 26% of the patients, negative in 38%, and non-diagnostic in 36%. Among the patients with a positive stress test result, 33% had symptoms, whereas 67% had silent myocardial ischaemia. The mortality rate was 7.1% among patients who did not have an exercise test and 1.7% [correction of 7.1%] for those with a positive test, 0.9% for those who had a negative test, and 1.3% for those who did not have a diagnostic test. In the adjusted analysis, symptomatic induced ischaemia, submaximal positive result, low work capacity, and abnormal systolic blood pressure were independent predictors of 6-month mortality (relative risks [RR] 2.54, 95% CI 1.27-5.08, 2.28, 1.17-4.45, 2.05, 1.23-3.42, and 1.86, 1.05-3.31, respectively). However, when these factors were tested simultaneously, only symptomatic induced ischaemia and low work capacity were confirmed as independent predictors of mortality (RR Cox 2.07, 95% CI 1.02-4.23 and 1.78, 1.06-2.99, respectively). Patients with a normal exercise response have an excellent medium-term prognosis and do not need further investigation. However, more evaluation should be devoted to the patients who cannot undergo exercise testing, because the potential to influence outcome appears to be much greater.

Aged↗
PubMed1995

Modulation of retinoblastoma gene in normal adult hematopoiesis: peak expression and functional role in advanced erythroid differentiation.

The retinoblastoma (RB) gene specifies a nuclear phosphoprotein (pRb 105), which is a prototype tumor suppressor inactivated in a variety of human tumors. Recent studies suggest that RB is also involved in embryonic development of murine central nervous and hematopoietic systems. We have investigated RB expression and function in human adult hematopoiesis--i.e., in liquid suspension culture of purified quiescent hematopoietic progenitor cells (HPCs) induced by growth factor stimulus to proliferation and unilinage differentiation/maturation through the erythroid or granulocytic lineage. In the initial HPC differentiation stages, the RB gene is gradually induced at the mRNA and protein level in both erythroid and granulopoietic cultures. In late HPC differentiation and then precursor maturation, RB gene expression is sustained in the erythroid lineage, whereas it is sharply downmodulated in the granulocytic series. Functional studies were performed by treatment of HPC differentiation culture with phosphorothioate antisense oligomer targeting Rb mRNA; coherent with the expression pattern, oligomer treatment of late HPCs causes a dose-dependent and selective inhibition of erythroid colony formation. These observations suggest that the RB gene plays an erythroid- and stage-specific functional role in normal adult hematopoiesis, particularly at the level of late erythroid HPCs.

Adult↗
PubMed1995

Dissection of the genetic programs of p53-mediated G1 growth arrest and apoptosis: blocking p53-induced apoptosis unmasks G1 arrest.

Employing the myeloblastic leukemia M1 cell line, which does not express endogenous p53, and genetically engineered variants, it was recently shown that activation of p53, using a p53 temperature-sensitive mutant transgene (p53ts), resulted in rapid apoptosis that was delayed by high level ectopic expression of bcl-2. In this report, advantage has been taken of these M1 variants to investigate the relationship between p53-mediated G1 arrest and apoptosis. Flow cytometric cell cycle analysis has provided evidence that activation of wild-type (wt) p53 function in M1 cells resulted in the induction of G1 growth arrest; this was clearly seen in the M1p53/bcl-2 cells because of the delay in apoptosis that unmasked p53-induced G1 growth arrest. This finding was further corroborated at the molecular level by analysis of the expression and function of key cell cycle regulatory genes in M1p53 versus M1p53/bcl-2 cells after the activation of wt p53 function; events that take place at early times during the p53-induced G1 arrest occur in both the M1p53 and the M1p53/bcl-2 cells, whereas later events occur only in the M1p53/bcl-2 cells, which undergo delayed apoptosis, thereby allowing the cells to complete G1 arrest. Finally, it was observed that a spectrum of p53 target genes implicated in p53-induced growth suppression and apoptosis were similarly regulated, either induced (gadd45, waf1, mdm2, and bax) or suppressed (c-myc and bcl-2), after activation of wt p53 function in M1p53 and M1p53/bcl-2 cells. Taken together, these findings show that wt p53 can simultaneously induce the genetic programs of both G1 growth arrest and apoptosis within the same cell type, in which the genetic program of cell death can proceed in either G1-arrested (M1p53/bcl-2) or cycling (M1p53) cells. These findings increase our understanding of the functions of p53 as a tumor suppressor and how alterations in these functions could contribute to malignancy.

Animals↗
PubMed1995

Technetium-99m sestamibi tomographic evaluation of residual ischemia after anterior myocardial infarction.

OBJECTIVES: This study investigated the value of sestamibi scintigraphy in assessing residual ischemia after anterior myocardial infarction. BACKGROUND: Serial imaging with sestamibi, the uptake and retention of which correlate with regional myocardial blood flow and viability, has been used to estimate salvaged myocardium and risk area after acute infarction. We recently documented that recovery of perfusion and contraction in the infarcted area may continue well after the subacute phase, suggesting myocardial hibernation. Some underestimation of viability in the setting of hibernating myocardium by sestamibi imaging has been reported. METHODS: We studied 58 patients in stable condition after Q wave anterior infarction. Regional perfusion and function were quantitatively assessed by sestamibi tomography and two-dimensional echocardiography at 4 to 6 weeks and at 7 months after infarction. In sestamibi polar maps, abnormal areas with tracer uptake > 2.5 SD below our reference values were computed at rest and after symptom-limited exercise. On two-dimensional echocardiography the ejection fraction and extent of rest wall motion abnormalities were assessed by a computerized system. All patients had coronary angiography between the two studies. RESULTS: At 7 months the extent of rest sestamibi defect was significantly reduced in 40 patients (69%, group 1) and unchanged in 18 (31%, group 2). Rest wall motion abnormalities and ventricular ejection fraction significantly improved in group 1 but not in group 2. Underlying coronary disease, patency of the infarct-related vessel and rest sestamibi defect extent at 5 weeks were comparable between the two groups. At 7 months, an increase in the reversible (stress-rest defect) tracer defect was observed in group 1 (p < 0.05) despite a smaller stress-induced hypoperfusion (p < 0.05). Reversible sestamibi defects and stress hypoperfusion were unchanged in group 2. In 38 (95%) of 40 group 1 patients, the area showing reversible sestamibi defects at 7 months matched the area showing fixed hypoperfusion at 5 weeks. CONCLUSIONS: The reduction in the rest tracer uptake defect that can occur late after infarction may affect the assessment of ischemic burden by sestamibi imaging early after anterior myocardial infarction.

Adult↗
PubMed1995

Cytokine induction of proliferation and expression of CDC2 and cyclin A in FDC-P1 myeloid hematopoietic progenitor cells: regulation of ubiquitous and cell cycle-dependent histone gene transcription factors.

To evaluate transcriptional mechanisms during cytokine induction of myeloid progenitor cell proliferation, we examined the expression and activity of transcription factors that control cell cycle-dependent histone genes in interleukin-3 (IL-3)-dependent FDC-P1 cells. Histone genes are transcriptionally upregulated in response to a series of cellular regulatory signals that mediate competency for cell cycle progression of the G1/S-phase transition. We therefore focused on factors that are functionally related to activity of the principal cell cycle regulatory element of the histone H4 promoter: CDC2, cyclin A, as well as RB- and IRF-related proteins. Comparisons were made with activities of ubiquitous transcription factors that influence a broad spectrum of promoters independent of proliferation or expression of tissue-specific phenotypic properties. Northern blot analysis indicates that cellular levels of cyclin A and CDC2 mRNAs increase when DNA synthesis and H4 gene expression are initiated, supporting involvement in cell cycle progression. Using gel-shift assays, incorporating factor-specific antibody and oligonucleotide competition controls, we define three sequential period following cytokine stimulation of FDC-P1 cells when selective upregulation of a subset of transcription factors is observed. In the initial period, the levels of SP1 and HiNF-P are moderately elevated; ATF, AP-1, and HiNF-M/IRF-2 are maximal during the second period; while E2F and HiNF-D, which contain cyclin A as a component, predominate during the third period, coinciding with maximal H4 gene expression and DNA synthesis. Differential regulation of H4 gene transcription factors following growth stimulation is consistent with a principal role of histone gene promoter elements in integrating cues from multiple signaling pathways that control cell cycle induction and progression. Regulation of transcription factors controlling histone gene promoter activity within the context of a staged cascade of responsiveness to cyclins and other physiological mediators of proliferation in FDC-P1 cells provides a paradigm for experimentally addressing interdependent cell cycle and cell growth parameters that are operative in hematopoietic stem cells.

Base Sequence↗