# GO Tutorial: Annotating A Paper

## Exercise IV

### Annotation - Answers

Thanks to Emily Dimmer for providing the annotations!

Page 13919, first paragraph

Few coactivators show tissue-specific expression. One of them is PGC-1, which
is expressed at high levels in tissues such as heart, skeletal muscle, kidney,
and brown fat. PGC-1 expression is induced also in a tissue-specific manner, in
response to particular physiological states such as exposure to cold or fasting.
Induction of PGC-1 in response to signals indicating metabolic needs of an
organism can then lead to the activation of pathways important for energy
homeostasis, such as adaptive thermogenesis, mitochondrial biogenesis, fatty acid
oxidation, and gluconeogenesis. PGC-1 interacts with and enhances the activity of
many nuclear receptors, like the peroxisome proliferator-activated receptors
(PPAR) alpha and gamma, TR, GR, ER-alpha, hepatocyte nuclear factor 4 (HNF4), as
well as nonreceptor transcription factors like the nuclear respiratory factor 1
(NRF1). A characteristic feature of PGC-1, not shared by other nuclear receptor
coactivators, is its C-terminal domain. It harbors sequence motifs typical of RNA
processing regulators and has been implicated in the regulation of pre-mRNA
splicing.

    response to cold ; GO:0009409
    response to starvation ; GO:0042594
    mitochondrion organization and biogenesis ; GO:0007005
    fatty acid oxidation ; GO:0019395
    gluconeogenesis ; GO:0006094
    pre-mRNA splicing factor activity ; GO:0008248

Page 13920, bottom of the page

...This region includes a RNA recognition motif (RRM), which has been
implicated in the regulation of RNA processing...

    RNA binding ; GO:0003723

Page 13921, last sentence of the first paragraph

Finally, consistent with the presence of nuclear localization signal
sequences, PERC is a nuclear protein.

    nucleus ; GO:0005634

Second column, about half way down

The one nuclear receptor where PERC functioned as a potent coactivator
was ER-alpha.

    estrogen receptor signaling pathway ; GO:0030520 [process]
    ligand-dependent nuclear receptor transcription coactivator activity ; GO:0030374 [function]

p13922, end of the first paragraph

In conclusion, PERC interacts via two motifs, NR1 and NR2, with a
ligand-dependent conformation of the ER-alpha AF2 domain.

    AF2 domain binding ; GO:0050682

Top of the second column

A fusion of PERC to the DBD of Gal4, which recruits PERC to a Gal4-responsive luciferase reporter, indeed activated transcription strongly.

    positive regulation of transcription ; GO:0045941

p13923, top of first column

It potently enhances the ligand-dependent activity of ER-alpha, while
having only minimal effects on the activity of the related receptor ER-beta or
other nuclear receptors tested here.

    ligand-dependent nuclear receptor transcription coactivator activity ; GO:0030374

p13924, second column, bottom of the page / p13925, top of page

PERC mRNA distribution is very similar to that of PGC-1. PGC-1 function in
heart, muscle, and liver may mediate physiological state signals to
tissue-specific transcriptional activation of proteins that regulate energy and
glucose homeostasis. For example, in response to exposure to cold, PGC-1
induces the expression of uncoupling proteins and stimulates energy expenditure
in brown fat and muscle, while in response to fasting, it stimulates
gluconeogenesis in liver.

    cell glucose homeostasis ; GO:0001678
    response to cold ; GO:0009409
    response to starvation ; GO:0042594
    gluconeogenesis ; GO:0006094

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