Stimulation of RNA Polymerase II Elongation by Chromosomal Protein HMG-14

Ding, Han‐Fei; Rimsky, Sylvie; Batson, S C; Bustin, Michael; Hansen, Ulla

doi:10.1126/science.8047885

Cited by 79 publications

(67 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Early studies suggested that the chromatin of actively transcribed globin gene is depleted of H1 and enriched in HMGNs (50). Likewise, in an in vitro chromatin assembly system HMGN1 alleviates H1-mediated inhibition of transcription from SV40 promoters (29). These findings correlate well with more recent findings indicating that in living cells HMGN proteins compete with H1 for chromatin binding sites (43).…”

Section: Comparison With Hmgn1supporting

confidence: 81%

Chromosomal Protein HMGN1 Enhances the Heat Shock-induced Remodeling of Hsp70 Chromatin

Belova

Postnikov

Furusawa

et al. 2008

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

The nucleosome-binding protein HMGN1 affects the structure and function of chromatin; however, its role in regulating specific gene expression in living cells is not fully understood. Here we use embryonic fibroblasts from Hmgn1 ؉/؉ and Hmgn1 ؊/؊ mice to examine the effect of HMGN1 on the heat shock-induced transcriptional activation of Hsp70, a well characterized gene known to undergo a rapid chromatin re-structuring during transcriptional activation. We find that loss of HMGN1 decreases the levels of Hsp70 transcripts at the early stages of heat shock. HMGN1 enhances the rate of heat shockinduced changes in the Hsp70 chromatin but does not affect the chromatin structure before induction, an indication that it does not predispose the gene to rapid activation. Heat shock elevates the levels of H3K14 acetylation in the Hsp70 chromatin of wild type cells more efficiently than in the chromatin of Hmgn1 ؊/؊ cells, whereas treatment with histone deacetylase inhibitors abrogates the effects of HMGN1 on the heat shock response. We suggest that HMGN1 enhances the rate of heat shock-induced H3K14 acetylation in the Hsp70 promoter, thereby enhancing the rate of chromatin remodeling and the subsequent transcription during the early rounds of Hsp70 activation when the gene is still associated with histones in a nucleosomal conformation.

show abstract

Section: Comparison With Hmgn1supporting

confidence: 81%

Chromosomal Protein HMGN1 Enhances the Heat Shock-induced Remodeling of Hsp70 Chromatin

Belova

Postnikov

Furusawa

et al. 2008

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…For example, nucleosomes have been described to impede transcriptional elongation (Izban and Luse 1991). Recently, HMG-14, a nonhistone chromosomal protein, has been reported to increase transcriptional elongation about fourfold in in vitro transcription reactions on nucleosomal templates (Ding et al 1994). Although HMG-14 and other nonhistone proteins are abundant nuclear proteins, some are found only in transcriptionally active regions {Weisbrod et al 1980).…”

Section: Elongation Rate As An Important Mechanism For Gene Regulationmentioning

confidence: 99%

Promoter-proximal pausing of RNA polymerase II defines a general rate-limiting step after transcription initiation.

Krumm¹,

Hickey²,

Groudine³

1995

Genes Dev.

205

173

View full text Add to dashboard Cite

We have shown previously that the majority of RNA polymerase II complexes initiated at the c-myc gene are paused in the promoter-proximal region, similar to observations in the Drosophila hspTO gene. Our analyses define the TATA box or initiator sequences in the c.myc gene as necessary components for the establishment of paused RNA polymerase II. Deletion of upstream sequences or even the TATA box does not influence significantly the degree of transcriptional initiation or pausing. Deletion of both the TATA box and sequences at the transcription initiation site, however, abolishes transcriptional pausing of transcription complexes but still allows synthesis of full-length RNA. Further analyses with synthetic promoter constructs reveal that the simple combination of upstream activator with TATA consensus sequences or initiator sequences act synergistically to recruit high levels of RNA polymerase II complexes. Only a minor fraction of these complexes escapes into regions further downstream. Several different trans-activation domains fused to GAL4-DNA-binding domains, including strong activators such as VP16, do not eliminate promoter-proximal pausing of RNA polymerase. Thus, we conclude that pausing of RNA polymerase I! is a common phenomenon in eukaryotic transcription and does not require complex promoter structures. Further analyses reveal that enhancers have a modest influence on transcription initiation and on release of transcription complexes out of the pause site but may function primarily to increase the elongation competence of transcription complexes.[Key Words: C-myc gene; promoter-proximal pausing; RNA polymerase II; transcription initiation; elongation; enhancer]Received November 30, 1994; revised version accepted January 26, 1995.The level of c-myc RNA is regulated largely through a mechanism that operates after transcription initiation. This conclusion is based on the observation that steadystate c-myc RNA levels decline significantly as cells differentiate, whereas transcriptional initiation, as measured in nuclear run-on assays, remains unchanged (Bentley and Groudine 1986; Eick and Bomkamm 1986; Nepveu and Marcu 1986; for review, see Krumm et al. 1993).Recent in vivo assays have demonstrated paused RNA polymerase II complexes at promoter-proximal regions of the c-myc gene. For example, in vivo footprinting with KMnO 4 as a reagent to detect single-stranded DNA residues within transcription bubbles revealed hyper-reactire sites around position +30. These results suggested that RNA polymerases pause in the promoter-proximal region around +30. Nuclear run-on experiments with short probes confirmed that the majority of RNA polymerases is located within the first 169 bp . In another study, nuclear run-on experiments with oligonucleotide probes as short as 50 bp also indi3Corresponding author.cated that the highest level of RNA polymerase II is within the promoter-proximal region between + 1 and +50 (Strobl and Eick 1992). Further experiments demonstrated that sequences 5' of +47 were sufficient to c...

show abstract

“…Thus, most likely the behavioral changes seen in mice with altered HMGN1 expression are not solely due to its effect on MeCP2 levels but rather to the global effect due to HMGN1 impact on gene expression. Indeed, in vitro chromatin studies indicated that HMGN1 affects the rate of transcription (5,13), and recent studies revealed that either up-or down-regulation of HMGN1 levels affect the expression of numerous genes, albeit most of the changes were relatively small (14).…”

Section: Hmgn1mentioning

confidence: 99%

“…The interaction of HMGN1 with nucleosomes, which is highly dynamic (7)(8)(9), modulates the structure of chromatin (5,6) and the levels of histone modifications (10,11), thereby playing a role in epigenetic regulation. HMGN1 affects chromatin functions including DNA repair (12) and transcription (13,14); however, its biological function is not fully understood.…”

Section: Hmgn1mentioning

confidence: 99%

The Chromatin-binding Protein HMGN1 Regulates the Expression of Methyl CpG-binding Protein 2 (MECP2) and Affects the Behavior of Mice

Abuhatzira

Shamir

Schones

et al. 2011

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Background: HMGN1 is a chromatin-binding protein that modulates the cellular transcription profile. Results: Mice that either overexpress or lack HMGN1 have altered behavioral phenotypes. HMGN1 is a negative regulator of MeCP2, a protein involved in neurodevelopmental disorders. Conclusion: Misregulation of HMGN1 protein levels lead to behavioral changes in mice. Significance: HMGN1 is an epigenetic factor that contributes to the development of neurodevelopmental disorders.

show abstract

Stimulation of RNA Polymerase II Elongation by Chromosomal Protein HMG-14

Cited by 79 publications

References 27 publications

Chromosomal Protein HMGN1 Enhances the Heat Shock-induced Remodeling of Hsp70 Chromatin

Chromosomal Protein HMGN1 Enhances the Heat Shock-induced Remodeling of Hsp70 Chromatin

Promoter-proximal pausing of RNA polymerase II defines a general rate-limiting step after transcription initiation.

The Chromatin-binding Protein HMGN1 Regulates the Expression of Methyl CpG-binding Protein 2 (MECP2) and Affects the Behavior of Mice

Contact Info

Product

Resources

About