Project: Research project

Project Details


DESCRIPTION: The goals of the proposed research are to advance our
understanding of the functions of the H1 linker histones and the relevance
of their diversity. H1 histones are thought to facilitate the folding of
chromatin into higher order structures and thereby influence gene expression
and other processes requiring access to DNA. Most of the knowledge about
the functions of the H1 histones has been derived from in vitro studies.
This proposal will analyze the functions of H1 histones in vivo in mice.
Mice and other mammals have at least 7 different subtypes of H1 histones
that differ considerably in their primary sequence and expression during
development. The working hypothesis to be tested in this proposal is that
different H1 subtypes contribute to establishing differences in vivo
chromatin structures and differences in gene regulation. The strategy for
studying the function of specific H1 subtypes is to generate and
characterize mice in which one or more H1 genes have been knocked out. Gene
inactivation will be used to 1) determine the effect of eliminating one H1
subtype on the phenotype and on gene expression patterns in specific tissue
and 2) to determine the effect of eliminating several H1 subtypes
simultaneously so as to generate animals in which several tissues contain
mostly one subtype or even a large deficiency in total linker histone
content. The mechanisms by which H1 histones participate in regulating
transcription will be analyzed by comparing the chromatin structure in the
vicinity of specific genes. The proposal will also characterize a new,
potentially novel H1 gene and attempt to identify other H1-related genes in
the mouse genome.
Effective start/end date4/1/987/31/16


  • Genetics
  • Medicine(all)
  • Molecular Biology
  • Immunology


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