Biomedical subjects

M Groudine

Publications and source records attributed to M Groudine.

130 records · Page 8Linked to original sources

PubMedDate not supplied

Alteration of c-myc chromatin structure by avian leukosis virus integration.

The most common sites of integration of the leukosis virus (ALV) long terminal repeat (LTR) in bursal lymphomas and derivative cell lines correspond to a region encompassed by two major hypersensitive sites in the 5' flanking region of the pre-integration, unrearranged c-myc gene. After integration of the ALV LTR, the major hypersensitive site within the avian c-myc oncogene region is within the proviral LTR, and the major hypersensitive sites normally found in uninfected cells 5' to the first c-myc coding exon are no longer detectable.

Animals↗

PubMedDate not supplied

Levels of c-myc oncogene mRNA are invariant throughout the cell cycle.

The steady-state messenger RNA levels of several genes increase when cells are stimulated to proliferate. The transcripts from one such gene, the proto-oncogene c-myc, increase approximately 20-fold shortly after cells are stimulated to proliferate and then decline before the onset of DNA synthesis. It has been inferred from these data that expression of c-myc may be specific to the G1 portion of the cell cycle. Alternatively, this transient increase in c-myc mRNA following the stimulation of quiescent cells could be the result of an activational event that renders the cells competent to enter the cell cycle. To distinguish between these possibilities, we performed experiments to determine whether the amount of c-myc mRNA fluctuates during the cell cycle in cells that are under constant stimulation to proliferate. Although c-myc mRNA does undergo a transient increase within 2 h of serum stimulation of quiescent serum-deprived cells, our results show that the level of c-myc mRNA is constant throughout the cell cycle and does not diminish in density-arrested cells maintained in the presence of serum growth factors. In contrast to c-myc, the mRNA levels of two other genes whose expression has been associated with cellular proliferation do show consistent variations within the cell cycle. Both thymidine kinase (TK) and histone 2b (H2b) mRNA levels increase during S phase in continuously growing cells and decrease when cell replication ceases in density-arrested cultures. Therefore, the transient increase in c-myc transcription following the activation of quiescent cells is not due to the type of cell cycle-dependent regulation characteristic of the TK and H2b genes.

Animals↗

PubMedDate not supplied

Expression of the c-myb proto-oncogene during cellular proliferation.

In several cell types, messenger RNA levels of the nuclear proto-oncogene c-myb vary as a function of cellular proliferation; a transient increase in c-myb steady-state mRNA, mediated by post-transcriptional mechanisms, occurs during cell-cycle progression. In contrast, both quiescent and proliferating immature thymocytes contain exceptionally high levels of c-myb mRNA as a consequence of increased c-myb transcription.

Animals↗

PubMedDate not supplied

A block to elongation is largely responsible for decreased transcription of c-myc in differentiated HL60 cells.

The c-myc gene product is a nuclear protein expressed in a wide variety of cell types. It has been implicated in the control of normal cell growth as well as transformation, but its exact function is unknown. When the human promyelocytic leukaemia cell line HL60 is treated with retinoic acid, the cells differentiate into granulocytes, and there is a reduction in steady state c-myc RNA of more than 10-fold. Nuclear runoff assays show that this reduction is caused by a corresponding decrease in the transcription of exon 2. However, only a minor decrease in exon 1 transcription is observed upon differentiation. In undifferentiated HL60 cells there is an approximately 3-fold molar excess of exon 1 transcription over exon 2, and this excess increases to about 15-fold in differentiated cells. This observation suggests that a major component of c-myc transcriptional down-regulation in HL60 cells is at the level of elongation rather than at the level of initiation. The position of the elongation block was mapped to the region of the boundary between exon 1 and intron 1. During HL60 differentiation, a DNase I hypersensitive site in the chromatin about 300 bases downstream of the 5' end of of intron 1 increases in intensity relative to other sites, possibly reflecting events associated with the termination of transcription. Our runoff analysis also revealed transcription of both strands immediately upstream of exon 1 in HL60 cells. The sense strand transcription of this region produces a novel c-myc RNA which initiates several hundred bases upstream of the previously defined promoters and is found in a variety of cell types.

Cell Differentiation↗