What's Up and Down with Histone Deacetylation and Transcription?

Pazin, Michael J.; Kadonaga, James T.

doi:10.1016/s0092-8674(00)80211-1

Cited by 803 publications

(555 citation statements)

References 13 publications

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“…It is common knowledge that HDACi not only deacetylate histones but also other proteins that are transcriptional regulators. 34 Two to ten percent of genes are believed to be regulated by histone acetylation and deacetylation, 35 but we do not know whether these compounds upregulate SMN2 by increasing histone acetylation at the SMN promoter, or by activating the acetylation state of a critical transcription factor. 17 Kernochan et al 36 observed that even though acetylated H3 and H4 histones predominated in the transcriptional origin of the SMN gene, VPA treatment led to acetylation in farupstream regions where there are usually fewer acetylated H3 and H4 histones.…”

Section: Discussionmentioning

confidence: 99%

Treatment of spinal muscular atrophy cells with drugs that upregulate SMN expression reveals inter- and intra-patient variability

et al. 2011

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Spinal muscular atrophy (SMA) is a genetic neuromuscular disorder caused by mutations in the SMN1 gene. The homologous copy (SMN2) is always present in SMA patients. SMN1 gene transcripts are usually full-length (FL), but exon 7 is spliced out in a high proportion of SMN2 transcripts (delta7) (D7). Advances in drug therapy for SMA have shown that an increase in SMN mRNA and protein levels can be achieved in vitro. We performed a systematic analysis of SMN expression in primary fibroblasts and EBV-transformed lymphoblasts from seven SMA patients with varying clinical severity and different SMN1 genotypes to determine expression differences in two accessible tissues (skin and blood). The basal expression of SMN mRNA FL and D7 in fibroblasts and lymphoblasts was analyzed by quantitative real-time PCR. The FL-SMN and FL/D7 SMN ratios were higher in control cells than in patients. Furthermore, we investigated the response of these cell lines to hydroxyurea, valproate and phenylbutyrate, drugs previously reported to upregulate SMN2. The response to treatments with these compounds was heterogeneous. We found both intra-patient and inter-patient variability even within haploidentical siblings, suggesting that tissue and individual factors may affect the response to these compounds. To optimize the stratification of patients in clinical trials, in vitro studies should be performed before enrolment so as to define each patient as a responder or non-responder to the compound under investigation.

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Section: Discussionmentioning

confidence: 99%

Treatment of spinal muscular atrophy cells with drugs that upregulate SMN expression reveals inter- and intra-patient variability

et al. 2011

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“…Hence, such corepressors are recruited to target promoters by proteinprotein interactions between a specific DNA-binding partner and the corepressor. For example, the mSin3 protein is a corepressor that is recruited to target promoters by the bHLH leucine-zipper repressor Mad as well as by unliganded nuclear receptor proteins, such as the thyroid hormone receptor (Pazin and Kadonaga 1997). In addition, mSin3 has intrinsic repressor activity and represses target gene promoters when directly bound to DNA by a heterologous DNA-binding domain.…”

Section: Groucho Proteins Act As Corepressors For Specific Active Repmentioning

confidence: 99%

“…The Groucho proteins may also work by other mechanisms in addition to, or instead of, the assembly of chromatin. Such mechanisms could include interaction with components of the basal transcription complex or the recruitment of other proteins with repressor or enzymatic activity, such as the HDAC1 histone deacteylase protein that is known to interact with other transcriptional repressors (Pazin and Kadonaga 1997). Because the Groucho proteins can repress both activated and basal transcription (Fisher et al 1996), they are unlikely to act via the quenching (Levine and Manley 1989) of the activation domains of transcriptional activators.…”

Section: Fisher and Caudymentioning

confidence: 99%

Groucho proteins: transcriptional corepressors for specific subsets of DNA-binding transcription factors in vertebrates and invertebrates

1998

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“…DNA digestion is performed as described (21), except digestion is stopped by placing samples in a dry ice/EtOH bath for 10 min. Digested DNA (10 fmol) is incubated with 50 fmol of [γ-32 P] ATP-labeled primer and primer extension is performed as described (21). As an example, see the footprint of the distal and middle vCREs see Fig.…”

Section: Deoxyribonuclease I (Dnase I) Primer Extension Footprintingmentioning

confidence: 99%

Biochemical analyses of transcriptional regulatory mechanisms in a chromatin context

Konesky

Laybourn

2007

Methods

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We have optimized a recombinant chromatin assembly system that properly incorporates core histones and histone H1 into a chromatin template containing a natural promoter sequence. This article provides a step-by-step procedure for expression and purification of the proteins required for assembling well-defined chromatin templates. We describe how the degree of chromatin assembly in the absence and presence of histone H1 is measured using topological analysis and the use of micrococcal nuclease digestion performed to confirm H1 incorporation and determine the quality of in vitro chromatin templates. Further we describe the use sucrose gradient ultracentrifugation to verify that no unincorporated H1 remains as a second means for deciding on the proper H1 to core histone ratio during assembly. Additionally, we discuss the use of both yeast and Drosophila NAP-1 (yNAP-1 and dNAP-1, respectively) in the assembly of H1-containing chromatin. Finally, we provide detailed description of functional assays for investigating the mechanism of transcriptional regulation in a chromatin context (transcription, histone acetyltransferase activity, and protein association with promoter-bound complexes using immobilized chromatin templates).

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What's Up and Down with Histone Deacetylation and Transcription?

Abstract: RbAp46 and RbAp48 are closely related proteins). Perhaps significantly, RbAp48 is associated with Department of Biology and Center for Molecular Genetics HDAC1 (Taunton et al., 1996) and is also a subunit of chromatin assembly factor 1 (for reviews, see Roth and

Cited by 803 publications

References 13 publications

Treatment of spinal muscular atrophy cells with drugs that upregulate SMN expression reveals inter- and intra-patient variability

Treatment of spinal muscular atrophy cells with drugs that upregulate SMN expression reveals inter- and intra-patient variability

Groucho proteins: transcriptional corepressors for specific subsets of DNA-binding transcription factors in vertebrates and invertebrates

Biochemical analyses of transcriptional regulatory mechanisms in a chromatin context

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