# FORMATION, STRUCTURE AND FUNCTION IN HETEROCHROMATIN

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 1994 · $226,277

## Abstract

The long-term objective of this proposal is to determine the mechanism
by which the packaging of a gene in heterochromatin leads to stable
inactivation. This type of "off" regulation is clearly of functional
important in chromosome imprinting, and may extend to the regulation of
the homeotic loci, whose on/off pattern is critical for normal develop-
ment in all higher organisms. Drosophila will be used throughout this
study because of the ease of manipulation and monitoring of Position
effect variegation, one type of epigenetic down-regulation that appears
to reflect the packaging of the test gene. We have identified a
heterochromatin-associated protein, HP1, which plays a role in this gene
inactivation; mutations in HP1 result in suppression of position effect
variegation in Drosophila. Our first aim is to identify proteins which
interact with HP1, using biochemical and genetic approaches. Interacting
proteins will be sought using (a) a genetic screen in Drosophila; (b)
coprecipitation with anti-HP1 antibodies; and (c) a screen in yeast that
requires protein-protein interactions to score a positive result (Fields
and Song, 1989, Nature 340, 245-246). In the genetic screen, missense
mutations, including temperature-sensitive alleles of HP1, are being
sought, as well as noncomplementing second-site mutations. Interacting
proteins identified will be characterized biochemically and genetically
to determine their role in heterochromatin formation.

In parallel with the study of HP1, we are carrying out studies of the
nucleosomal and higher order packaging of transgenes inserted into
heterochromatin using P-element mediated transformation. Two different
genes are being used, hsp26, a heat shock gene whose 5' upstream
regulatory region is normally preset in an accessible chromatin structure
prior to gene activation, and a CAT reporter gene under the control of
glucocorticoid response elements, a gene likely to be characteristic of
those whose 5' upstream regulatory region is packaged in a nucleosomal
array and must be remodeled for activation. We will characterize the
chromatin structure of these genes when they are packaged in
heterochromatin, in comparison to their packaging in euchromatin, in
order to learn more about the inactivation process. Having such specific
test genes in a heterochromatin environment will also be invaluable in
assessing the role of the chromosomal proteins identified above. These
studies should move us much closer to an understanding of the nature and
regulatory role of higher order chromatin structure.

## Key facts

- **NIH application ID:** 2198970
- **Project number:** 5R01HD023844-07
- **Recipient organization:** WASHINGTON UNIVERSITY
- **SAM.gov UEI:** L6NFUM28LQM5
- **Principal Investigator:** Sarah C.R. ELGIN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $226,277
- **Award type:** 5
- **Project period:** 1987-12-01 → 1998-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2198970

## Citation

> US National Institutes of Health, RePORTER application 2198970, FORMATION, STRUCTURE AND FUNCTION IN HETEROCHROMATIN (5R01HD023844-07). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2198970. Licensed CC0.

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