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2015 ; 11
(12
): e1005701
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Recruitment of Mediator Complex by Cell Type and Stage-Specific Factors Required
for Tissue-Specific TAF Dependent Gene Activation in an Adult Stem Cell Lineage
#MMPMID26624996
Lu C
; Fuller MT
PLoS Genet
2015[Dec]; 11
(12
): e1005701
PMID26624996
show ga
Onset of terminal differentiation in adult stem cell lineages is commonly marked
by robust activation of new transcriptional programs required to make the
appropriate differentiated cell type(s). In the Drosophila male germ line stem
cell lineage, the switch from proliferating spermatogonia to spermatocyte is
accompanied by one of the most dramatic transcriptional changes in the fly, as
over 1000 new transcripts turn on in preparation for meiosis and spermatid
differentiation. Here we show that function of the coactivator complex Mediator
is required for activation of hundreds of new transcripts in the spermatocyte
program. Mediator appears to act in a sequential hierarchy, with the testis
activating Complex (tMAC), a cell type specific form of the Mip/dREAM general
repressor, required to recruit Mediator subunits to the chromatin, and Mediator
function required to recruit the testis TAFs (tTAFs), spermatocyte specific
homologs of subunits of TFIID. Mediator, tMAC and the tTAFs co-regulate
expression of a major set of spermatid differentiation genes. The Mediator
subunit Med22 binds the tMAC component Topi when the two are coexpressed in S2
cells, suggesting direct recruitment. Loss of Med22 function in spermatocytes
causes meiosis I maturation arrest male infertility, similar to loss of function
of the tMAC subunits or the tTAFs. Our results illuminate how cell type specific
versions of the Mip/dREAM complex and the general transcription machinery
cooperate to drive selective gene activation during differentiation in stem cell
lineages.
|*Spermatogenesis
[MESH]
|Adult Stem Cells/cytology/metabolism
[MESH]
|Animals
[MESH]
|Cell Differentiation/genetics
[MESH]
|Cell Lineage
[MESH]
|Drosophila Proteins/*genetics
[MESH]
|Drosophila melanogaster/genetics/growth & development
[MESH]