Involvement of the cell cycle-regulated nuclear factor HiNF-D in cell growth control of a human H4 histone gene during hepatic development in transgenic mice
Journal Article
·
· Proceedings of the National Academy of Sciences of the United States of America; (United States)
- Univ. of Massachusetts Medical Center, Worcester (United States)
- Whitehead Inst., Cambridge, MA (United States)
Regulation of the cell cycle-controlled histone gene promoter factor HiNF-D was examined in vivo. Proliferative activity was measured by DNA replication-dependent histone mRNA levels, and HiNF-D binding activity was found to correlate with cell proliferation in most tissues. Furthermore, HiNF-D is down-regulated during hepatic development, reflecting the onset of differentiation and quiescence. The contribution of transcription to histone gene expression was directly addressed in transgenic mice by using a set of fusion constructs containing a human H4 histone gene promoter linked to three different genes. Transgene expression in both fetal and adult mice paralleled endogenous mouse histone mRNA levels in most tissues, consistent with this promoter conferring developmental, cell growth-related transcriptional regulation. The results suggest that HiNF-D is stringently regulated in vivo in relation to cell growth and support a primary role for HiNF-D in the proliferation-specific expression of H4 histone genes in the intact animal. Further, the data presented here provide an example in which apparent tissue specificity of gene expression reflects the proliferative state of various tissues and demonstrate that multiple levels of histone gene regulation are operative in vivo.
- OSTI ID:
- 5078782
- Journal Information:
- Proceedings of the National Academy of Sciences of the United States of America; (United States), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (United States) Vol. 88:6; ISSN 0027-8424; ISSN PNASA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMAL CELLS
ANTI-INFECTIVE AGENTS
ANTIBIOTICS
BIOCHEMISTRY
CARBON 14 COMPOUNDS
CARBON COMPOUNDS
CELL CYCLE
CELL PROLIFERATION
CHEMISTRY
CHLORAMPHENICOL
DNA REPLICATION
DRUGS
GENE REGULATION
GENE REPRESSORS
HISTONES
LABELLED COMPOUNDS
LIVER CELLS
NUCLEIC ACID REPLICATION
NUCLEOPROTEINS
ORGANIC COMPOUNDS
PROTEINS
SOMATIC CELLS
TRANSCRIPTION
59 BASIC BIOLOGICAL SCIENCES
ANIMAL CELLS
ANTI-INFECTIVE AGENTS
ANTIBIOTICS
BIOCHEMISTRY
CARBON 14 COMPOUNDS
CARBON COMPOUNDS
CELL CYCLE
CELL PROLIFERATION
CHEMISTRY
CHLORAMPHENICOL
DNA REPLICATION
DRUGS
GENE REGULATION
GENE REPRESSORS
HISTONES
LABELLED COMPOUNDS
LIVER CELLS
NUCLEIC ACID REPLICATION
NUCLEOPROTEINS
ORGANIC COMPOUNDS
PROTEINS
SOMATIC CELLS
TRANSCRIPTION