Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “effector genes”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 163 records · Page 9Linked to original sources
PubMed2001

Differences in gene expression in muscle-invasive bladder cancer: a comparison of Italian and American patients.

OBJECTIVE: To seek differences in gene expression in the primary muscle-invasive bladder cancers of two cohorts of patients having different survival rates. An Italian group treated by transurethral resection of the bladder tumor (TURBT) and neo-adjuvant chemotherapy using methotrexate, vinblastine, adriamycin and cisplatin (M-VAC) followed by TURBT, partial cystectomy or radical cystectomy (75% 3-year survival) was compared to an American cohort treated by radical cystectomy (51% 3-year survival). METHODS: Immunohistochemistry was used to examine the protein expression levels of three genes that act at the G1/S cell cycle checkpoint, p53, p21/waf-1/cip1 (a downstream effector gene in the p53 pathway) and Rb, plus a major inhibitor of apoptosis, Bcl-2. RESULTS: For the bladder cancers of the Italian patient cohort, there was a significantly higher rate of p53 immunopositivity (93 vs. 63%, p = 0.002) and a significantly lower rate of Rb loss (25 vs. 54%, p = 0.009). In bivariate analysis, 72% of Italian tumors were immunopositive for both p53 and p21 (p53+/p21+) vs. 49% for the American tumors. The subset of Italian patients with p53+/p21+ tumors were more frequently disease-free (stage pT0) following chemotherapy and were less likely to fail therapy than those with p53+/p21- tumors (p = 0.0357). Loss of Rb staining was associated with a decreased 5-year survival in the Italian, but not in the American patients. CONCLUSIONS: (1) Significant differences in the expression of the p53, p21 and Rb genes were found between the 2 groups of patients. (2) Italian patients with p53+/p21+ tumors had significantly lower recurrence rates after TURBT and chemotherapy than those having p53+/p21- tumors. (3) Absence of p21 immunopositivity in the Italian tumors may identify alterations in the p53 pathway that predict poor outcome.

Gene Expression Regulation, Neoplastic↗
PubMed1996

Effect of decreased fte-1 gene expression on protein synthesis, cell growth, and transformation.

The fte-1 gene, previously cloned in our laboratory as a putative v-fos transformation effector gene (C.J. Kho and H. Zarbl, Proc. Natl. Acad. Sci. USA, 89: 2200-2204, 1992), has been shown to encode ribosomal protein S3a. Comparison of fte-1 expression in a variety of normal and transformed cells indicated that elevated expression of fte-1 mRNA was frequently associated with transformation of rodent and human cells. In an effort to understand how monoallelic disruption of fte-1 is able to block v-fos-induced cell transformation, we examined the pattern of fte-1 expression during cell cycle progression and determined its effects on protein synthesis and cell growth. In synchronously cultured human fibroblasts, fte-1 mRNA was found to accumulate in cells undergoing DNA synthesis, suggesting that its expression is correlated with S-phase progression. fte-1 does not function as a dominant oncogene because ectopic overexpression of fte-1 in normal Rat-1 fibroblasts failed to induce cell transformation. However, the expression of antisense fte-1 resulted in growth inhibition. Monoallelic disruption of the fte-1 gene in v-fos-transformed Rat-1 fibroblasts resulted not only in loss of the transformed phenotype but also in a decreased rate of protein synthesis due to decreased polysome formation. Taken together, these results indicate that the accumulation of ribosomal subunits and the rate of protein synthesis are important modulators of neoplastic transformation and cell growth.

Animals↗
PubMed2004

Genetic screening of Hrp type III-related pathogenicity genes controlled by the HrpB transcriptional activator in Ralstonia solanacearum.

As in many other Gram-negative phytopathogenic bacteria, the Hrp type III secretion system is essential for the pathogenicity of Ralstonia solanacearum on host plants. The expression of most of the type III effector genes previously isolated from R. solanacearum is co-regulated with those of hrp genes by an AraC-type transcriptional activator, HrpB. In order to isolate type III-related pathogenicity genes, we screened hrpB-regulated genes in R. solanacearum. Using a transposon-based system, we isolated 30 novel hpx (hrpB-dependent expression) genes outside the hrp gene cluster. Most of the hpx genes contain a PIP (plant-inducible promoter) box-like motif in their putative promoter regions. Seven hpx genes encoded homologues of known type III effectors and type III-related proteins found in other animal and plant pathogens. Four encoded known enzymes, namely, glyoxalase I, Nudix hydrolase, spermidine synthase and transposase. Interestingly, six hpx genes encoded two types of leucine-rich repeat (LRR) protein. Products of the remaining genes did not show any significant homology to known proteins. We also identified two novel hrpB-regulated genes, hpaZ and hpaB, downstream of hrpY in the hrp cluster. The hpaB gene of R. solanacearum, but not hpaZ, was required for both the pathogenicity and ability to induce hypersensitive reaction on plants. We show that a hpaB null mutant still produces Hrp pili on the cell surface although it shows a typical Hrp-defective phenotype on plants.

Bacterial Proteins↗
PubMed2006

Whole-genome expression profiling defines the HrpL regulon of Pseudomonas syringae pv. tomato DC3000, allows de novo reconstruction of the Hrp cis clement, and identifies novel coregulated genes.

Pseudomonas syringae pv. tomato DC3000 is a model pathogen of tomato and Arabidopsis that uses a hypersensitive response and pathogenicity (Hrp) type III secretion system (T3SS) to deliver virulence effector proteins into host cells. Expression of the Hrp system and many effector genes is activated by the HrpL alternative sigma factor. Here, an open reading frame-specific whole-genome microarray was constructed for DC3000 and used to comprehensively identify genes that are differentially expressed in wild-type and deltahrpL strains. Among the genes whose differential regulation was statistically significant, 119 were upregulated and 76 were downregulated in the wild-type compared with the deltahrpL strain. Hierarchical clustering revealed a subset of eight genes that were upregulated particularly rapidly. Gibbs sampling of regions upstream of HrpL-activated operons revealed the Hrp promoter as the only identifiable regulatory motif and supported an iterative refinement involving real-time polymerase chain reaction testing of additional HrpL-activated genes and refinements in a hidden Markov model that can be used to predict Hrp promoters in P. syringae strains. This iterative bioinformatic-experimental approach to a comprehensive analysis of the HrpL regulon revealed a mix of genes controlled by HrpL, including those encoding most type III effectors, twin-arginine transport (TAT) substrates, other regulatory proteins, and proteins involved in the synthesis or metabolism of phytohormones, phytotoxins, and myo-inositol. This analysis provides an extensively verified, robust method for predicting Hrp promoters in P. syringae genomes, and it supports subsequent identification of effectors and other factors that likely are important to the host-specific virulence of P. syringae.

Bacterial Proteins↗
PubMed1997

Regulatory sequences of Arabidopsis drive reporter gene expression in nematode feeding structures.

In the quest for plant regulatory sequences capable of driving nematode-triggered effector gene expression in feeding structures, we show that promoter tagging is a valuable tool. A large collection of transgenic Arabidopsis plants was generated. They were transformed with a beta-glucuronidase gene functioning as a promoter tag. Three T-DNA constructs, pGV1047, p delta gusBin19, and pMOG553, were used. Early responses to nematode invasion were of primary interest. Six lines exhibiting beta-glucuronidase activity in syncytia induced by the beet cyst nematode were studied. Reporter gene activation was also identified in galls induced by root knot and ectoparasitic nematodes. Time-course studies revealed that all six tags were differentially activated during the development of the feeding structure. T-DNA-flanking regions responsible for the observed responses after nematode infection were isolated and characterized for promoter activity.

Animals↗
PubMed2025

Effectidor II: a pan-genomic AI-based algorithm for the prediction of type III secretion system effectors.

MOTIVATION: Type III secretion systems are used by many Gram-negative bacteria to inject type 3 effectors (T3Es) directly into eukaryotic cells, promoting disease or provoking immune response. Because of these opposing evolutionary forces, T3E repertoires often vary within taxonomic groups. Identifying the full effector gene repertoire in genomes of related individuals is crucial for determining core and specialized effectors, understanding the disease dynamics, and developing appropriate management strategies against pathogens. It can also help uncover novel T3Es that have recently emerged in a population. Our previously published Effectidor web server successfully addressed the challenge of identifying T3Es in a single bacterial genome. Here, we enriched the web server with various novel capabilities, including the identification of T3Es from multiple genome sequences simultaneously. RESULTS: We present Effectidor II, a web server that relies on machine learning to predict T3E-encoding genes within bacterial pan-genomes. We demonstrate the benefit of learning based on features extracted from the entire sequences comprising the pan-genome and report a novel T3E discovered by it in Xanthomonas euroxanthea. AVAILABILITY AND IMPLEMENTATION: Effectidor II is available at: https://effectidor.tau.ac.il and the source code is available at: https://github.com/naamawagner/Effectidor. A stand-alone version of Effectidor II is available at: https://github.com/naamawagner/Effectidor/tree/StandAlone. The source code for the standalone version and the data used in this work are also provided in https://doi.org/10.5281/zenodo.15081636.

Type III Secretion Systems↗
PubMed1993

Interaction of six global transcription regulators in expression of manganese superoxide dismutase in Escherichia coli K-12.

Transcription of the sodA gene of Escherichia coli, which encodes manganese superoxide dismutase, is governed by six global regulators: the product of the soxRS locus (superoxide response) and mutated alleles of the soxQ locus (such as cfxB) act as activators; the products of the fur (ferric uptake regulation), arcA (aerobic regulation control), and fnr (fumarate nitrate reductase) genes and the integration host factor (IHF) negatively regulate sodA. The action of these effectors on the sodA promoter was investigated by using chromosomal sodA-lacZ operon fusions with intact or deleted promoters, different environmental conditions, and strains carrying different combinations of null mutations in the effector genes. The data allow us to assign target regions in the sodA promoter for activation by SoxRS and CfxB and for repression by Fur and ArcA. In aerobiosis, activation of sodA transcription by SoxRS was compatible with CfxB activation or Fur repression, whereas cfxB and fur controls were mutually exclusive. Repression by Fnr appeared, at least in part, to be ArcA dependent. IHF enhanced aerobic Fur repression, and in the absence of Fur, it enhanced anaerobic repression by ArcA. The DNA targets for Fur (encompassing the -35 region) and ArcA (from and downstream of the -35 region) appear to overlap, suggesting that Fur and ArcA repressions are mutually exclusive. Fur (in response to the iron pool) or ArcA, acting with Fnr and IHF (in response to the redox state of the cells), can block anaerobic sodA-lacZ expression with about equivalent efficiencies. The possible biological significance of this result is discussed.

Bacterial Outer Membrane Proteins↗
PubMed2001

Genetic determinants that influence hypoxia-induced apoptosis.

The p53 tumour suppressor gene is capable of activating both death receptor and mitochondrial-signalled forms of apoptotic cell death in response to diverse stimuli. Studies have suggested that impairment of the mitochondrial-signalled Apaf/caspase 9 pathway and not the death receptor Fas pathway results in almost complete resistance to apoptotic cell death induced by a low oxygen environment. However, it is unclear how p53 signals the activation of this pathway and whether it is through already identified p53 effector genes such as the pro-apoptotic gene bax, or through novel effectors such as BNIP-3/BNIP-3L. Comparison of cell lines genetically matched at the bax, cytochrome c, apaf, caspase 9 and caspase 3 loci indicated that except for bax, all of these genes were essential for hypoxia induced apoptosis both in cell culture and in transplanted tumours. These data imply that cytochrome c plays a pivotal role in signalling cell death by apoptosis under hypoxic conditions, and that the release of cytochrome c is independent of both Bax and p53. In contrast to cytochrome c, p53 modulates the magnitude of apoptosis under hypoxic conditions, but in itself is not required for the activation of the caspase cascade.

Aerobiosis↗
PubMed1996

Abrogation of p53 function affects gadd gene responses to DNA base-damaging agents and starvation.

The tumor suppressor p53 is required for induction of its downstream effector genes such as GADD45 and CIP1/WAF1 by ionizing radiation (IR). This response is probably mediated through defined p53 binding sites located in the promoter of CIP1/WAF1 and in the third intron of GADD45. In contrast, the gadd gene stress response to base-damaging agents, such as methylmethane sulfonate (MMS) or UV radiation, or medium depletion (starvation) occurs in all mammalian cells examined to date regardless of p53 status for both GADD45 and also GADD153, which is not IR-responsive in many lines with functional p53. These agents strongly induce the p53 protein and raise the possibility that, although p53 is not required for the typical "gadd" response to these agents, p53 may contribute to these non-IR stress responses. This possibility was confirmed by the finding that disruption of p53 function by transfection with dominant-negative vectors expressing HPV E6, mutant p53, or SV40 T Ag reduced the induction of GADD45 and GADD153 as measured by increases in mRNA and protein levels in human lines with wild-type p53. Similarly, induction of these genes by MMS or UV radiation was consistently stronger in the parental mouse embryo fibroblasts compared to cells derived from mice where both p53 alleles had been deleted. Similar qualitative responses were also seen for CIP1/WAF1. In agreement with reduced induction of p53-regulated genes, the G1 checkpoint activated by MMS or UV radiation was markedly abrogated in p53-wt human MCF-7 breast carcinoma cells by E6 expression. Interestingly, induction of reporter constructs driven by the GADD45 or GADD153 promoters was substantially reduced in human cells transfected with mutant p53 or E6 expression vectors or in cells lacking p53 following treatment with MMS, UV radiation, or starvation. Because neither promoter is inducible by IR, and neither contains a strong p53 binding site, these results indicate that p53 has a synergistic or cooperative role in these non-IR stress responses for both GADD45 and GADD153, and that this role is not mediated through identifiable p53-binding sites.

Animals↗
PubMed2005

Genomic effect of vitamin 'C' and statins within human mononuclear cells involved in atherogenic process.

Deregulated crosstalk within nuclear receptor/transcription factor family, comprising of peroxisome proliferator-activated receptors (PPARs) and liver X receptor-alpha (LXR-alpha), can give rise to cooperativity between lipid peroxidation and inflammation leading to atherogenic process. The present study addressed to explore the effect of statins and vitamin 'C' on transcriptional expression of genes coding for this nuclear receptor/transcription factor family within mononuclear cells revealed for the first time that both mevastatin and vitamin 'C' have common action in that they significantly downregulate the expression of PPARs (alpha, gamma) genes and upregulate LXR-alpha gene expression as compared to the control. The similar phenomenon was observed in mononuclear cells obtained from coronary heart disease (CHD) patients who were receiving atorvastatin treatment (20 mg HS). Further, the observed upregulatory effect of LXR-alpha gene expression was in conformity with the downregulatory effect of LXR-alpha on its effector gene matrix metalloproteinase-9. Based on these results, we propose that LXR-alpha-dependent signaling pathway may be a crucial target for the therapeutic intervention in human CHD, and in addition to statins, vitamin 'C' deserves a close scrutiny for the treatment of CHD.

Animals↗
PubMed2004

New approaches for in silico identification of cytokine-modified beta cell gene networks.

Beta cell dysfunction and death in type 1 diabetes mellitus (T1DM) is caused by direct contact with activated macrophages and T lymphocytes and by exposure to soluble mediators secreted by these cells, such as cytokines and nitric oxide. Cytokine-induced apoptosis depends on the expression of pro- and anti-apoptotic genes that remain to be characterized. Using microarray analyses, we identified several transcription factor and "effector" gene networks regulated by interleukin-1beta and/or interferon-gamma in beta cells. This suggests that beta cell fate following exposure to cytokines is a complex and highly regulated process, depending on the duration and severity of perturbation of key gene networks. In order to draw correct conclusions from these massive amounts of data, we need to utilize novel bioinformatics and statistical tools. Thus, we are presently performing in silico analysis for the localization of binding sites for the transcription factor NF-kappaB (previously shown to be pivotal for beta cell apoptosis) in 15 temporally related gene clusters, identified by time-course microarray analysis. In silico analysis is based on a broad range of computational techniques used to detect motifs in a DNA sequence corresponding to the binding site of a transcription factor. These computer-based findings must be validated by use of positive and negative controls, and by "ChIP on chip" analysis. Moreover, new statistical approaches are required to decrease false positive findings. These novel approaches will constitute a "proof of principle" for the integrated use of bioinformatics and functional genomics in the characterization of relevant cytokine-regulated beta cell gene networks leading to beta cell apoptosis in T1DM.

Animals↗
PubMed2005

Attenuated rabies virus activates, while pathogenic rabies virus evades, the host innate immune responses in the central nervous system.

Rabies virus (RV) induces encephalomyelitis in humans and animals. However, the pathogenic mechanism of rabies is not fully understood. To investigate the host responses to RV infection, we examined and compared the pathology, particularly the inflammatory responses, and the gene expression profiles in the brains of mice infected with wild-type (wt) virus silver-haired bat RV (SHBRV) or laboratory-adapted virus B2C, using a mouse genomic array (Affymetrix). Extensive inflammatory responses were observed in animals infected with the attenuated RV, but little or no inflammatory responses were found in mice infected with wt RV. Furthermore, attenuated RV induced the expression of the genes involved in the innate immune and antiviral responses, especially those related to the alpha/beta interferon (IFN-alpha/beta) signaling pathways and inflammatory chemokines. For the IFN-alpha/beta signaling pathways, many of the interferon regulatory genes, such as the signal transduction activation transducers and interferon regulatory factors, as well as the effector genes, for example, 2'-5'-oligoadenylate synthetase and myxovirus proteins, are highly induced in mice infected with attenuated RV. However, many of these genes were not up-regulated in mice infected with wt SHBRV. The data obtained by microarray analysis were confirmed by real-time PCR. Together, these data suggest that attenuated RV activates, while pathogenic RV evades, the host innate immune and antiviral responses.

Animals↗
PubMed2003

Use of microarray analysis to unveil transcription factor and gene networks contributing to Beta cell dysfunction and apoptosis.

The beta cell fate following immune-mediated damage depends on an intricate pattern of dozens of genes up- or downregulated in parallel and/or sequentially. We are utilizing microarray analysis to clarify the pattern of gene expression in primary rat beta cells exposed to the proapoptotic cytokines, IL-1beta and/or IFN-gamma. The picture emerging from these experiments is that beta cells are not passive bystanders of their own destruction. On the contrary, beta cells respond to damage by activating diverse networks of transcription factors and genes that may either lead to apoptosis or preserve viability. Of note, cytokine-exposed beta cells produce and release chemokines that may contribute to the homing and activation of T cells and macrophages during insulitis. Several of the effects of cytokines depend on the activation of the transcription factor, NF-kappaB. NF-kappaB blocking prevents cytokine-induced beta cell death, and characterization of NF-kappaB-dependent genes by microarray analysis indicated that this transcription factor controls diverse networks of transcription factors and effector genes that are relevant for maintenance of beta cell differentiated status, cytosolic and ER calcium homeostasis, attraction of mononuclear cells, and apoptosis. Identification of this and additional "transcription factor networks" is being pursued by cluster analysis of gene expression in insulin-producing cells exposed to cytokines for different time periods. Identification of complex gene patterns poses a formidable challenge, but is now technically feasible. These accumulating evidences may finally unveil the molecular mechanisms regulating the beta cell "decision" to undergo or not apoptosis in early T1DM.

Apoptosis↗
PubMed1991

Genetic control of the metastatic phenotype.

Transfection experiments indicate that a number of genes can induce or suppress the metastatic phenotype. These genes include ten oncogenes, plasminogen activator, and three suppressor genes. The biochemical mechanism(s) whereby each of these genes alters the metastatic phenotype is poorly understood. Hypotheses concerning the coordinate regulation of metastasis-effector genes, and the relationship of gene expression in metastasis to that in embryonic development are discussed.

Animals↗
PubMed1998

Cytotoxic lymphocyte gene expression in peripheral blood leukocytes correlates with rejecting renal allografts.

BACKGROUND: We have shown previously that heightened expression of the cytotoxic lymphocyte (CL) effector genes perforin (P), granzyme B (GB), and Fas ligand (FasL), is closely correlated with acute allograft rejection, particularly when two or more target genes are up-regulated. METHODS: We used quantitative reverse transcription-polymerase chain reaction to analyze CL gene expression from peripheral blood leukocytes (PBLs) and renal allograft biopsies in 31 paired samples of PBLs and renal tissue from 25 renal allograft recipients. Our aims were (1) to determine whether the expression of CL gene expression in PBLs correlates with expression of these genes in renal allograft biopsy tissue and (2) to determine whether CL gene expression in PBLs correlates with the histological diagnosis. RESULTS: Coordinate gene expression in PBLs and acutely rejecting allografts was found in 9/11 (82%) for P, 07/11 (64%) for GB, and 10/11 (91%) for FasL. Coordinate absence was found in 15/20 (75%) for P, 17/20 (85%) for GB, and 16/20 (80%) for FasL in nonrejecting allografts. Furthermore, up-regulation of any two genes in PBLs correlated with pathological diagnosis of rejection with excellent positive (100%) and negative (95%) predictive values. CONCLUSION: Coordinate CL gene expression in PBLs and the allograft is usually detected. CL gene expression in PBLs is closely associated with a pathologic diagnosis of rejection. CL gene expression in PBLs may serve as a noninvasive method of monitoring for renal allograft rejection.

Adult↗
PubMed2004

Serial peripheral blood interleukin-18 and perforin gene expression measurements for prediction of acute kidney graft rejection.

BACKGROUND: We and others have shown that expression of the cytotoxic T-lymphocyte effector gene perforin in the peripheral blood is a strong predictor of acute rejection in the early posttransplant period. In the present study we investigated whether interleukin (IL)-18, an immunostimulatory gene that up-regulates perforin-dependent cytotoxicity and promotes tissue damage through other noncytotoxic T-lymphocyte mechanisms alone or in combination with perforin gene expression, may serve as a better predictor of renal allograft rejection in the first weeks after transplantation. METHODS: Peripheral blood was collected twice weekly, and gene expression was measured using real-time polymerase chain reaction. RESULTS: Recipients with acute rejection (n = 17) showed higher levels of perforin and IL-18 transcript on days 5 to 7, 8 to 10, and 11 to 13, compared with patients without rejection (n = 37, P < 0.01 in all cases). Rejection diagnosis using gene expression criteria was possible 1 to 32 days before traditional diagnosis (median 11 days). High specificity was associated with IL-18 expression (72%-93%), and high sensitivity was associated with perforin expression (63%-90%). Positive predictive value was optimized (78%-100%) by using combined up-regulation in both genes as a diagnostic criterion (double-positive). Using high expression in "either or both" genes as a diagnostic criterion yielded high sensitivity (82%-91%) and negative predictive value (91%-96%). CONCLUSIONS: Our data indicate that combined perforin and IL-18 gene expression measurements are useful tools for the recognition of graft rejection in its earliest stages. Serial measurements could be implemented as a monitoring system to identify patients at higher risk of rejection, making them candidates for biopsy or prophylactic increases in immunosuppression.

Acute Disease↗
PubMed2006

Transcriptional profiling of apoptotic pathways in batch and fed-batch CHO cell cultures.

Chinese Hamster ovary (CHO) cells are regarded as one of the "work-horses" for complex biotherapeutics production. In these processes, loss in culture viability occurs primarily via apoptosis, a genetically controlled form of cellular suicide. Using our "in-house" developed CHO cDNA array and a mouse oligonucleotide array for time profile expression analysis of batch and fed-batch CHO cell cultures, the genetic circuitry that regulates and executes apoptosis induction were examined. During periods of high viability, most pro-apoptotic genes were down-regulated but upon loss in viability, several early pro-apoptotic signaling genes were up-regulated. At later stages of viability loss, we detected late pro-apoptotic effector genes such as caspases and DNases being up-regulated. This sequential regulation of apoptotic genes showed that DNA microarrays could be used as a tool to study apoptosis. We found that in batch and fed-batch cultures, apoptosis signaling occurred primarily via death receptor- and mitochondria-mediated signaling pathways rather than endoplasmic reticulum-mediated signaling. These insights provide a greater understanding of the regulatory circuitry of apoptosis during cell culture and allow for subsequent targeting of relevant apoptosis signaling genes to prolong cell culture.

Animals↗
PubMed1999

Differentiation: A central topic in developmental and cell biology.

The concept of "differentiation" encompasses all processes leading to differently specialized cell types, beginning with the progressive divergence of developmental pathways and ending with the successive programming and final elaboration of each particular cell type. Guidance and positional information are provided by external cues, by differentially allotted cytoplasmic determinants such as mRNA for transcription factors, and by cascades of intercellular signals. Eventually cell type specific selector genes, such as the muscle cell determining MyoD/myogenin genes and neural key genes (e. g., achaete scute-C, neurogenin), are switched on which control entire sets of subordinate effector genes. In multiplying cells "cell heredity" based on an epigenetic cellular memory enables transmission of the cell type determining program from parental to daughter cells. This memory can be based on autocatalytic self-activation of cell type specific selector genes and on the enduring action of gene groups such as the Polycomb and thrithorax complexes that code for proteins which bind to DNA sequences called cellular memory modules. These modules confer permanent accessibility (potentiation) or inaccessibility (silencing) upon many different gene loci on the chromosomes.

Animals↗