Heterochromatin is a critical component of higher eukaryotic genomes and plays a role in chromosome segregation, recombination, and gene expression. Constitutive heterochromatin in Drosophila is characterized by the presence of transposable elements, hypoacetylated histone tails, methylated histone H3 at lysine 9, and association of HP1. The RNAi-machinery and small RNAs that correspond to repetitious elements also play a role in forming heterochromatin. Our overall goal is to dissect the process of heterochromatin formation by investigating components of the pathway required for targeting/initiation, maintenance, and spreading. To this end, we will examine the relative abundance of repeat associated small RNAs and determine the impact of mutations in the RNAi-machinery and heterochromatin components on these RNAs. Furthermore, we will test the capacity of an animal genome to target heterochromatin formation in trans through expression of a hairpin RNA corresponding to the target regions. If successful, this assay will allow us to dissect components involved in initiation and maintenance versus spreading and will be used to screen for mutations that impact heterochromatin formation. An assay for disruption of heterochromatic marks in tissue culture cells will also be developed, which could be used as an alternative screen for novel components of the heterochromatin formation pathway. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32GM078833-02
Application #
7275308
Study Section
Special Emphasis Panel (ZRG1-F08-G (20))
Program Officer
Portnoy, Matthew
Project Start
2006-08-01
Project End
2009-07-31
Budget Start
2007-08-01
Budget End
2008-07-31
Support Year
2
Fiscal Year
2007
Total Cost
$48,796
Indirect Cost
Name
Washington University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Huisinga, Kathryn L; Riddle, Nicole C; Leung, Wilson et al. (2016) Targeting of P-Element Reporters to Heterochromatic Domains by Transposable Element 1360 in Drosophila melanogaster. Genetics 202:565-82
Brower-Toland, Brent; Riddle, Nicole C; Jiang, Hongmei et al. (2009) Multiple SET methyltransferases are required to maintain normal heterochromatin domains in the genome of Drosophila melanogaster. Genetics 181:1303-19
Huisinga, Kathryn L; Elgin, Sarah C R (2009) Small RNA-directed heterochromatin formation in the context of development: what flies might learn from fission yeast. Biochim Biophys Acta 1789:3-16