GSBS Student Publications

Title

Control of cell cycle regulated histone genes during proliferation and differentiation

GSBS Program

Biochemistry & Molecular Pharmacology

UMMS Affiliation

Graduate School of Biomedical Sciences; Department of Cell Biology

Date

3-1-1996

Document Type

Article

Medical Subject Headings

Animals; Cell Cycle; Cell Differentiation; Cell Division; DNA; *Gene Expression Regulation; Histones; Humans; Promoter Regions (Genetics)

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

Proliferation is a requirement during the initial stages of cell and tissue specialization. In most biological systems the down-regulation of proliferation is necessary for initiation of key steps in the differentiation process. We have examined regulatory mechanisms controlling expression of the cell cycle-dependent histone genes, which are functionally coupled with DNA synthesis, in proliferating cells and during the onset of differentiation in several phenotypes including adipocytes. In proliferating cells transcription of the histone genes is up-regulated at the onset of S phase. We have identified a histone H4 proximal promoter element, designated Site II, that mediates cell cycle transcriptional control. The factor interacting with Site II include cdc2, cyclin A, an RB-related protein and interferon regulatory factors (IRFs). Mutational analysis indicates that the distal part of Site II is critical for cell cycle regulation. Equally important for the developmental transcriptional control, histone gene expression is repressed when differentiation is initiated. In vivo, we have established loss of Site II occupancy by regulatory proteins; in vitro, factor binding to Site II is not observed post-proliferatively. Deletion analysis indicates that proximal Site II mediates the differentiation response of H4 gene transcription in adipocytes.

Rights and Permissions

Citation: Int J Obes Relat Metab Disord. 1996 Mar;20 Suppl 3:S84-90.

Related Resources

Link to Article in PubMed

Journal Title

International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity

PubMed ID

8680483

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