Download Expression of yolk protein genes in liver Beekman, Johanna

University of Groningen
Expression of yolk protein genes in liver
Beekman, Johanna Margaretha
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Publication date:
1990
Link to publication in University of Groningen/UMCG research database
Citation for published version (APA):
Beekman, J. M. (1990). Expression of yolk protein genes in liver s.n.
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93
Summary
Themainsubject of this thesis is the transcriptionalregulationof tho
chickenvitellogeninll (Vtg) and apo very low density lipoproteinll
(apoVLDLll)
genes. These genes code for (precursor) yolk proteins and
are only expressedin the liver of a layinghen. The transcription is
dependenton tho fomalesex hormoneoestradiol.In the
completely
oviductthe synthesis of egg white proteins is also controlledby
oestradiol.The obsorvationthat two different sets of genes are under
controlof the samehormonebut expressedin different tissues gives
rise to one of the mainquestion ]n biology;what is the mechanism
of
tissue-specificand hormone-induced
expressionof eukaryotic gones?.
Chapter1 briefly reviewsthe regulationof gene expressionin
eukaryotes.The other chaptersdescriberesults obtainedin experiments
to unravelthe mechanism
of oestrogen-inducedand liver-specific
genes in chicken.
expression
of the Vtg and apoVLDLll
ln Chapter2 we describethe isolationand cultivationof chicken
hepatocytes(CEHcells). Thesecells transcribe their
embryonic
Vtg gene in an oestradiol-dependentway. By a simple
endogenous
calcium-phosphate
coprecipitationmethodDNAcan be introducedinto
thosecells and expressed.lncreasingthe oestrogen receptor
concentrationartificiatly,makesthese cells a good host for gene
transfer experimentsin the study of oestrogen-regulatedgene
expression.Weused the CEHcells to identify regulatory regions of the
Vtg gene (Chapter3). In this chapter we confirmthat the oestrogen
responseelementaround position -620 is involvodin the oestrogeninducibleexpressionof the Vtg gene. This is not the only oestrogen
responsiveregion identified.Another region harboursoestrogeninducibility,althoughan EREsequencecannot be discoveredin this
region.Sincethis region doos not function in another oestrogen
responsivecell, we do not believethat the oestrogen receptor can bind
to this rogion directly. lt either needs the help of another protein to
bindin this region or the other protein functions as a "bridge"to bring
the receptor that binds to the EREaround position -620 close to the
promoter.ln this chapter we also describethe presencoof an enhancer
regionthat may bind a NFl-like protein and/or a C/EBP-likeprotein.
Chapters4 and 5 describe the gene transfer experimentsperformedin
the search for regulatory elementsof the apoVLDLllgen. Analysisof the
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S'-Ílanking region revealed the presonce of two oestrogen response
elom€nts,that are necessary for the oestrogen-inducible expression of
the coupled CAT gene. Several other sequences appear to be involved.
Described are, el€mentsthat may bind the liver-specific transcription
Íactors HNF-1 or LF-A1, or elementsthat bind the CCAAT/enhancer
binding protein (Chapter 6).
It is clear from tho rosults presented in this thesis that regulation of
gene expression is a complexprocess, that involves transcription
factors that can bind to regulatory regions in several genes. The
specific combinationof binding sites and the presence of specific
transcription factors in the cell probably determine the strict tissuespocific, developmental-stagespecific or inducible expression of a gene.
The study on the mechanismsof gene regulation has made an enormous
progress for the last decade. Increasingour knowledgeon gene
regulation at the molecularlevel is not only intellectually satisfying, but
also vitally important in the battle against diseases such as cancer, in
which tho control of gene expression is altered or lost.