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Full Abstracts – CHROMATIN AND EPIGENETICS
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The Unusual Features of Active Genes on Drosophila melanogaster Chromosome Four: Reinterpreting the Roles of Chromatin Modifications.
Sarah
CR Elgin
1
, Nicole C Riddle
1
, Tingting Gu
1
, Youngsook L Jung
2
, Monica Sentmanat
1
, modENCODE Drosophila Chromatin Consortium. 1) Washington
Univ, St Louis, MO; 2) Harvard Medical School, Boston, MA.
The small fourth (dot) chromosome of Drosophila melanogaster exhibits overall characteristics of a heterochromatic domain, including high levels of
H3K9me2/3 and HP1a, but contains ~80 genes in its 1.2 Mb banded portion. Mapping of histone modifications and chromosomal proteins in S2 and BG3
cells shows that these genes have unique characteristics, distinctive from active genes in either euchromatin or pericentric heterochromatin. H3K9me2/3 and
HP1a are depleted at the TSSs (transcription start sites) of active fourth chromosome genes; the TSSs, as expected, are occupied by H3K4me2/3 and RNA
pol II. However, POF (painting of fourth), HP1a, and H3K9me3 are found at high levels across the gene body. There is no evidence of euchromatin
“islands” supporting expression. Rather reporter sites permissive for expression appear to be those regulated by the Polycomb system in at least some cell
types. Fourth chromosome genes exhibit the same range of expression levels seen in other domains, but there are few if any associated with a paused
polymerase. The continued presence of HP1a and H3K9me3 at active genes results in a shift in association patterns, with H3K9me2 now being unique in its
stronger correlation with inactive genes. Depletion of POF results in loss of HP1a from fourth chromosome gene bodies, but HP1a continues to be present in
the pericentric heterochromatin and at repeat clusters on the fourth, indicating a dual targeting mechanism for HP1a association with the fourth chromosome.
These findings challenge our prior interpretations of the roles of some histone modifications in gene regulation and focus attention on the modifications at
the TSS. Supported by NIH grants U01HG0004258 to GH Karpen and R01 GM068388 to SCRE.