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Developmental regulation of transcription by a tissue-specific TAF homolog.

ABSTRACT: Alternate forms of the general transcription machinery have been described in several tissues or cell types. However, the role of tissue-specific TBP-associated factors (TAF(II)s) and other tissue-specific transcription components in regulating differential gene expression during development was not clear. Here we show that the cannonball gene of Drosophila encodes a cell type-specific homolog of a more ubiquitously expressed component of the general transcription factor TFIID. cannonball is required in vivo for high level transcription of a set of stage- and tissue-specific target genes during male gametogenesis. Regulation of transcription by cannonball is absolutely required for spermatogenesis, as null mutations block meiotic cell cycle progression and result in a complete failure of spermatid differentiation. Our results demonstrate that cell type-specific TAF(II)s play an important role in developmental regulation of gene expression.

SUBMITTER: Hiller MA

PROVIDER: S-EPMC312677 | biostudies-literature | 2001 Apr

REPOSITORIES: biostudies-literature

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Developmental regulation of transcription by a tissue-specific TAF homolog.

Hiller M A MA Lin T Y TY Wood C C Fuller M T MT

Genes & development 20010401 8

Alternate forms of the general transcription machinery have been described in several tissues or cell types. However, the role of tissue-specific TBP-associated factors (TAF(II)s) and other tissue-specific transcription components in regulating differential gene expression during development was not clear. Here we show that the cannonball gene of Drosophila encodes a cell type-specific homolog of a more ubiquitously expressed component of the general transcription factor TFIID. cannonball is req ...[more]

PMID: 11316795

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Project description:BACKGROUND:Identifying DNA sequences (enhancers) that direct the precise spatial and temporal expression of developmental control genes remains a significant challenge in the annotation of vertebrate genomes. Locating these sequences, which in many cases lie at a great distance from the transcription start site, has been a major obstacle in deciphering gene regulation. Coupling of comparative genomics with functional validation to locate such regulatory elements has been a successful method in locating many such regulatory elements. But most of these studies looked either at a single gene only or the whole genome without focusing on any particular process. The pressing need is to integrate the tools of comparative genomics with knowledge of developmental biology to validate enhancers for developmental transcription factors in greater detail RESULTS:Our results show that near four different genes (nkx3.2, pax9, otx1b and foxa2) in zebrafish, only 20-30% of highly conserved DNA sequences can act as developmental enhancers irrespective of the tissue the gene expresses in. We find that some genes also have multiple conserved enhancers expressing in the same tissue at the same or different time points in development. We also located non-conserved enhancers for two of the genes (pax9 and otx1b). Our modified Bacterial artificial chromosome (BACs) studies for these 4 genes revealed that many of these enhancers work in a synergistic fashion, which cannot be captured by individual DNA constructs and are not conserved at the sequence level. Our detailed biochemical and transgenic analysis revealed Foxa1 binds to the otx1b non-conserved enhancer to direct its activity in forebrain and otic vesicle of zebrafish at 24 hpf. CONCLUSION:Our results clearly indicate that high level of functional conservation of genes is not necessarily associated with sequence conservation of its regulatory elements. Moreover certain non conserved DNA elements might have role in gene regulation. The need is to bring together multiple approaches to bear upon individual genes to decipher all its regulatory elements.

Dataset Information

Developmental regulation of transcription by a tissue-specific TAF homolog.

Publications

Developmental regulation of transcription by a tissue-specific TAF homolog.

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