Abstract：
:Since the identification of a metazoan counterpart to yeast Mediator nearly 15 years ago, a convergent body of biochemical and molecular genetic studies have confirmed their structural and functional relationship as an integrative hub through which regulatory information conveyed by signal activated transcription factors is transduced to RNA polymerase II. Nonetheless, metazoan Mediator complexes have been shaped during evolution by substantive diversification and expansion in both the number and sequence of their constituent subunits, with important implications for the development of multicellular organisms. The appearance of unique interaction surfaces within metazoan Mediator complexes for transcription factors of diverse species-specific origins extended the role of Mediator to include an essential function in coupling developmentally coded signals with precise gene expression output sufficient to specify cell fate and function. The biological significance of Mediator in human development, suggested by genetic studies in lower metazoans, is emphatically illustrated by an expanding list of human pathologies linked to genetic variation or aberrant expression of its individual subunits. Here, we review our current body of knowledge concerning associations between individual Mediator subunits and specific pathological disorders. When established, molecular etiologies underlying genotype-phenotype correlations are addressed, and we anticipate that future progress in this critical area will help identify therapeutic targets across a range of human pathologies.
journal_name
Semin Cell Dev Bioljournal_title
Seminars in cell & developmental biologyauthors
Spaeth JM,Kim NH,Boyer TGdoi
10.1016/j.semcdb.2011.07.024subject
Has Abstractpub_date
2011-09-01 00:00:00pages
776-87issue
7eissn
1084-9521issn
1096-3634pii
S1084-9521(11)00112-1journal_volume
22pub_type
杂志文章,评审abstract：:Differences between sexes of the same species in lifespan and aging rate are widespread. While the proximal and evolutionary causes of aging are well researched, the factors that contribute to sex differences in these traits have been less studied. The striking diversity of nematodes provides ample opportunity to stud...
journal_title：Seminars in cell & developmental biology
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journal_title：Seminars in cell & developmental biology
pub_type： 杂志文章,评审
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journal_title：Seminars in cell & developmental biology
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journal_title：Seminars in cell & developmental biology
pub_type： 杂志文章,评审
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journal_title：Seminars in cell & developmental biology
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journal_title：Seminars in cell & developmental biology
pub_type： 杂志文章,评审
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journal_title：Seminars in cell & developmental biology
pub_type： 杂志文章,评审
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pub_type： 杂志文章,评审
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journal_title：Seminars in cell & developmental biology
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journal_title：Seminars in cell & developmental biology
pub_type： 杂志文章,评审
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journal_title：Seminars in cell & developmental biology
pub_type： 杂志文章,评审
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更新日期：2015-05-01 00:00:00
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journal_title：Seminars in cell & developmental biology
pub_type： 杂志文章,评审
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更新日期：2010-10-01 00:00:00
