# The formation of Heterochromatin on evolving Y chromosomes

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA BERKELEY · 2020 · $438,421

## Abstract

Most eukaryotes harbor a high proportion of transposable elements (TEs) in their genomes. Heterochromatin, a condensed chromatin
state found at domains enriched for TEs and other repetitious elements, is important for silencing TEs and maintaining the integrity of the
genome.
Significant portions of eukaryotic genomes, including the Y chromosome, are heterochromatic, made
up largely of repetitive sequences and possessing a distinctive chromatin structure associated with
gene silencing. Heterochromatic regions have a high repeat content and are characterized by specific
histone modifications, but the primary sequence elements that define specific chromosomal domains
as preferred sites of heterochromatin assembly are not well understood. In addition, recent work has
shown that the composition and organization of Drosophila heterochromatin is spatially
heterogeneous and dynamic, and a variety of cellular pathways and molecular components create
genetically inert heterochromatin, but only a subset of these components has been characterized.
Our proposal aims to dissect the cis- and trans-acting cellular mechanisms involved in
heterochromatin formation, by studying the genome-wide establishment of heterochromatin during
early development in different wildtype and transgenic Drosophila strains and species. Recent studies
suggest that small RNAs ⎯ possibly derived from transposable elements (TEs) ⎯ or specialized
DNA-binding zinc finger proteins contribute to heterochromatin targeting. Using a combination of
comparative sequence analysis, gene expression studies, small RNA profiling and ChIP-seq
experiments across development to map histone modifications associated with heterochromatin and
genome interaction maps, we will characterize the spatiotemporal heterogeneity of genome-wide
heterochromatin establishment across development in Drosophila melanogaster and D. miranda, and
catalog the establishment and maturation of inert chromatin in 3D during early development. This
will reveal which sequences serve as nucleation sites for inactive chromatin, and how silencing
chromatin spreads across the genome. The initial establishment of heterochromatin is driven by RNA
and protein components that are maternally deposited into the fertilized egg. We will utilize the
wealth of D. melanogaster resources to study heterochromatin formation in early embryos by depleting
maternally deposited candidate genes involved in establishing heterochromatin in the developing
embryo.
Integrating our results across aims will provide a full picture of how heterochromatin is established in
the early embryo, whether the initial establishment of closed chromatin proceeds in a sequential
manner, and how it spreads across the repetitive regions of the genome. We will dissect the
heterogeneous and dynamic composition of Drosophila heterochromatin across development and in
embryos where components of the heterochromatin pathway are depleted using transgenic
approaches. This will provi...

## Key facts

- **NIH application ID:** 9853628
- **Project number:** 5R01GM101255-06
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Doris Bachtrog
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $438,421
- **Award type:** 5
- **Project period:** 2015-01-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9853628

## Citation

> US National Institutes of Health, RePORTER application 9853628, The formation of Heterochromatin on evolving Y chromosomes (5R01GM101255-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9853628. Licensed CC0.

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