MYC directly transactivates CR2/CD21, the receptor of the Epstein-Barr virus, enhancing the viral infection of Burkitt lymphoma cells.

MYC is an oncogenic transcription factor dysregulated in about half of total human tumors. While transcriptomic studies reveal more than 1000 genes regulated by MYC, a much smaller fraction of genes is directly transactivated by MYC. Virtually all Burkitt lymphoma (BL) carry chromosomal translocations involving MYC oncogene.

A novel role of MNT as a negative regulator of REL and the NF-κB pathway.

MNT, a transcription factor of the MXD family, is an important modulator of the oncoprotein MYC. Both MNT and MYC are basic-helix-loop-helix proteins that heterodimerize with MAX in a mutually exclusive manner, and bind to E-boxes within regulatory regions of their target genes. While MYC generally activates transcription, MNT represses it.

The MNT transcription factor autoregulates its expression and supports proliferation in MYC-associated factor X (MAX)-deficient cells.

The MAX network transcriptional repressor (MNT) is an MXD family transcription factor of the basic helix-loop-helix (bHLH) family. MNT dimerizes with another transcriptional regulator, MYC-associated factor X (MAX), and down-regulates genes by binding to E-boxes. MAX also dimerizes with MYC, an oncogenic bHLH transcription factor.

A Genetic Dissection of Natural Variation for Stomatal Abundance Traits in .

Stomatal abundance varies widely across natural populations of , and presumably affects plant performance because it influences water and CO exchange with the atmosphere and thence photosynthesis and transpiration. In order to determine the genetic basis of this natural variation, we have analyzed a recombinant inbred line (RIL) population derived from the wild accession Ll-0 and the reference strain Landsberg (L), which show low and high stomatal abundance, respectively. Quantitative trait locus (QTL) analyses of stomatal index, stomatal density, and pavement cell density measured in the adaxial cotyledon epidermis, identified five loci.

Suppression of BCL6 function by HDAC inhibitor mediated acetylation and chromatin modification enhances BET inhibitor effects in B-cell lymphoma cells.

Multiple genetic aberrations in the regulation of BCL6, including in acetyltransferase genes, occur in clinically aggressive B-cell lymphomas and lead to higher expression levels and activity of this transcriptional repressor. BCL6 is, therefore, an attractive target for therapy in aggressive lymphomas. In this study romidepsin, a potent histone deacetylase inhibitor (HDACi), induced apoptosis and cell cycle arrest in Burkitt and diffuse large B-cell lymphoma cell lines, which are model cells for studying the mechanism of action of BCL6.

A Mutation in the bHLH Domain of the SPCH Transcription Factor Uncovers a BR-Dependent Mechanism for Stomatal Development.

The asymmetric cell divisions necessary for stomatal lineage initiation and progression in Arabidopsis () require the function of the basic helix-loop-helix (bHLH) transcription factor (). Mutants lacking do not produce stomata or lineages. Here, we isolated a new allele carrying a point mutation in the bHLH domain that displayed normal growth, but had an extremely low number of sometimes clustered stomata in the leaves, whereas the hypocotyls did not have any stomata.

Myc and cell cycle control.

Soon after the discovery of the Myc gene (c-Myc), it became clear that Myc expression levels tightly correlate to cell proliferation. The entry in cell cycle of quiescent cells upon Myc enforced expression has been described in many models. Also, the downregulation or inactivation of Myc results in the impairment of cell cycle progression.

Timely expression of the Arabidopsis stoma-fate master regulator MUTE is required for specification of other epidermal cell types.

Epidermal differentiation in Arabidopsis thaliana aerial organs involves stomatal lineage development. Lineages derive from meristemoids, which arise from asymmetric divisions of protodermal cells. Each meristemoid divides repeatedly in an inward spiral before it transits to a guard mother cell (GMC) that produces the stoma, leaving a trail of surrounding stomatal lineage ground cells (SLGCs) that eventually differentiate into endoreplicated pavement cells.

MYC oncogene in myeloid neoplasias.

MYC is a transcription factor that regulates many critical genes for cell proliferation, differentiation, and biomass accumulation. MYC is one of the most prevalent oncogenes found to be altered in human cancer, being deregulated in about 50 % of tumors. Although MYC deregulation has been more frequently associated to lymphoma and lymphoblastic leukemia than to myeloid malignancies, a body of evidence has been gathered showing that MYC plays a relevant role in malignancies derived from the myeloid compartment.

Roles of constitutive photomorphogenic 10 in Arabidopsis stomata development.

Stomata are epidermal bi-celled structures that differentiate within special cell lineages initiated by a subset of protodermal cells. Recently, we showed that the Arabidopsis photomorphogenic repressor COP10 controls specific cell-lineage and cell-signaling developmental mechanisms in stomatal lineages. Loss-of-function cop10-1 mutant cotyledons and leaves produced (in the light and in the dark) abundant stomatal clusters, but nonlineage epidermal cells were not affected.

A cell cycle role for the epigenetic factor CTCF-L/BORIS.

CTCF is a ubiquitous epigenetic regulator that has been proposed as a master keeper of chromatin organisation. CTCF-like, or BORIS, is thought to antagonise CTCF and has been found in normal testis, ovary and a large variety of tumour cells. The cellular function of BORIS remains intriguing although it might be involved in developmental reprogramming of gene expression patterns.

Transcription factors Sp1 and p73 control the expression of the proapoptotic protein NOXA in the response of testicular embryonal carcinoma cells to cisplatin.

Testicular germ cell tumors (TGCTs) are highly responsive to and curable by cisplatin-based chemotherapy even in advanced stages. We have studied the molecular mechanisms involved in the induction of apoptosis in response to cisplatin, and found that proapoptotic Noxa is transcriptionally up-regulated following cisplatin exposure, even in the absence of p53, in NTERA2 cisplatin-sensitive cells but not in 1411HP-resistant cells. Blockade of Noxa reduced the apoptotic response of embryonal carcinoma (EC) NTERA2 cells to cisplatin.

The male germ cell gene regulator CTCFL is functionally different from CTCF and binds CTCF-like consensus sites in a nucleosome composition-dependent manner.

Background: CTCF is a highly conserved and essential zinc finger protein expressed in virtually all cell types. In conjunction with cohesin, it organizes chromatin into loops, thereby regulating gene expression and epigenetic events. The function of CTCFL or BORIS, the testis-specific paralog of CTCF, is less clear.

p21 as a transcriptional co-repressor of S-phase and mitotic control genes.

It has been previously described that p21 functions not only as a CDK inhibitor but also as a transcriptional co-repressor in some systems. To investigate the roles of p21 in transcriptional control, we studied the gene expression changes in two human cell systems. Using a human leukemia cell line (K562) with inducible p21 expression and human primary keratinocytes with adenoviral-mediated p21 expression, we carried out microarray-based gene expression profiling.

Dynamic analysis of epidermal cell divisions identifies specific roles for COP10 in Arabidopsis stomatal lineage development.

Stomatal development in Arabidopsis thaliana has been linked to photoreceptor-perceived light through several components of the photomorphogenic switch, whose lack of function is often seedling-lethal. CONSTITUTIVE PHOTOMORPHOGENIC 10 (COP10) is an important component of this switch, its loss of function producing stomatal clusters. Exploiting the reduced lethality of the cop10-1 mutant we characterized the developmental basis of its stomatal phenotype.

Myc roles in hematopoiesis and leukemia.

Hematopoiesis is a process capable of generating millions of cells every second, as distributed in many cell types. The process is regulated by a number of transcription factors that regulate the differentiation along the distinct lineages and dictate the genetic program that defines each mature phenotype. Myc was first discovered as the oncogene of avian leukemogenic retroviruses; it was later found translocated in human lymphoma.

MYC in chronic myeloid leukemia: induction of aberrant DNA synthesis and association with poor response to imatinib.

Untreated chronic myeloid leukemia (CML) progresses from chronic phase to blastic crisis (BC). Increased genomic instability, deregulated proliferation, and loss of differentiation appear associated to BC, but the molecular alterations underlying the progression of CML are poorly characterized. MYC oncogene is frequently deregulated in human cancer, often associated with tumor progression.

Natural variation in stomatal abundance of Arabidopsis thaliana includes cryptic diversity for different developmental processes.

Background And Aims: Current understanding of stomatal development in Arabidopsis thaliana is based on mutations producing aberrant, often lethal phenotypes. The aim was to discover if naturally occurring viable phenotypes would be useful for studying stomatal development in a species that enables further molecular analysis.

Methods: Natural variation in stomatal abundance of A.

CTCF regulates the local epigenetic state of ribosomal DNA repeats.

Background: CCCTC binding factor (CTCF) is a highly conserved zinc finger protein, which is involved in chromatin organization, local histone modifications, and RNA polymerase II-mediated gene transcription. CTCF may act by binding tightly to DNA and recruiting other proteins to mediate its various functions in the nucleus. To further explore the role of this essential factor, we used a mass spectrometry-based approach to screen for novel CTCF-interacting partners.

Nuclear targeting of a bacterial integrase that mediates site-specific recombination between bacterial and human target sequences.

TrwC is a bacterial protein involved in conjugative transfer of plasmid R388. It is transferred together with the DNA strand into the recipient bacterial cell, where it can integrate the conjugatively transferred DNA strand into its target sequence present in the recipient cell. Considering that bacterial conjugation can occur between bacteria and eukaryotic cells, this protein has great biotechnological potential as a site-specific integrase.

p21(Cip1) confers resistance to imatinib in human chronic myeloid leukemia cells.

Imatinib is a Bcr-Abl inhibitor used as first-line therapy of chronic myeloid leukemia (CML). p21(Cip1), initially described as a cell cycle inhibitor, also protects from apoptosis in some models. We describe that imatinib down-regulates p21(Cip1) expression in CML cells.

Inhibition of cell differentiation: a critical mechanism for MYC-mediated carcinogenesis?

Despite its early discovery and relevance in cancer, the mechanisms by which MYC brings about tumorigenic transformation have not been clarified. MYC elicits a variety of biological activities, the proliferation promotion being the best studied. However, inhibition of cell differentiation was one of the first MYC activities described.