Nucleosome core binding region of chromosomal protein HMG-17 acts as an independent functional domain

Crippa, Massimo P.; Alfonso, Pedro J.; Bustin, Michael

doi:10.1016/0022-2836(92)90833-6

Cited by 69 publications

(76 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The function of HMGNs depends on their ability to bind two high affinity sites on the nucleosome (12), using a conserved nucleosome-binding domain (NBD) (9,12,13). Elucidation of the structural basis of this interaction has proven to be challenging because HMGNs are intrinsically disordered and their nucleosome-binding domains interact with the nucleosome core ( Fig.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Architecture of the high mobility group nucleosomal protein 2-nucleosome complex as revealed by methyl-based NMR

Kato

Ingen

Zhou

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

166

189

View full text Add to dashboard Cite

Chromatin structure and function are regulated by numerous proteins through specific binding to nucleosomes. The structural basis of many of these interactions is unknown, as in the case of the high mobility group nucleosomal (HMGN) protein family that regulates various chromatin functions, including transcription. Here, we report the architecture of the HMGN2-nucleosome complex determined by a combination of methyl-transverse relaxation optimized nuclear magnetic resonance spectroscopy (methyl-TROSY) and mutational analysis. We found that HMGN2 binds to both the acidic patch in the H2A-H2B dimer and to nucleosomal DNA near the entry/exit point, "stapling" the histone core and the DNA. These results provide insight into how HMGNs regulate chromatin structure through interfering with the binding of linker histone H1 to the nucleosome as well as a structural basis of how phosphorylation induces dissociation of HMGNs from chromatin during mitosis. Importantly, our approach is generally applicable to the study of nucleosome-binding interactions in chromatin.

show abstract

mentioning

confidence: 99%

“…Elucidation of the structural basis of this interaction has proven to be challenging because HMGNs are intrinsically disordered and their nucleosome-binding domains interact with the nucleosome core ( Fig. S1) (13), precluding the use of histone peptide models (14). Attempts to grow crystals of the HMGN2-nucleosome complex were so far unsuccessful.…”

mentioning

confidence: 99%

Architecture of the high mobility group nucleosomal protein 2-nucleosome complex as revealed by methyl-based NMR

Kato

Ingen

Zhou

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

166

189

View full text Add to dashboard Cite

show abstract

“…HMG14 and HMG17 are small (---10 kD), highly charged proteins that interact with high affinity to two distinct sites in nucleosomal cores (Albright et al 1980;Mardian et al 1980;Sandeen et al 1980;Shick et al 1985;Cook et al 1986;Crippa et al 1992Crippa et al , 1993Alfonso et al 1994). Moreover, HMG14/17 proteins bind with higher affinity to core particles than to naked DNA (Sandeen et al 1980).…”

mentioning

confidence: 99%

HMG17 is a chromatin-specific transcriptional coactivator that increases the efficiency of transcription initiation.

Paranjape¹,

Krumm²,

Kadonaga³

1995

Genes Dev.

View full text Add to dashboard Cite

We have examined the effect of HMG17 on transcription by RNA polymerase II by the assembly and analysis of HMG17-containing chromatin templates consisting of regularly spaced nucleosomal arrays. Structural analysis of the chromatin indicated that HMG17 is incorporated into chromatin in a physiological manner with the full complement of core histones. The transcriptional studies revealed that HMG17 stimulates transcription in conjunction with the sequence-specific activator GAL4-VP16. This effect was observed with chromatin, but not with non-nucleosomal templates, and required the presence of HMG17 during chromatin assembly. The incorporation of HMG17 into chromatin resulted in a 7-to 40-fold stimulation of GAL4-VP16-activated transcription to levels that were comparable to those observed with histone-free DNA templates. In contrast, transcription from HMG17-containing chromatin was not detectable in the absence of GAL4--VP16 or with a GAL4 derivative [GAL4(1-147)] lacking the VP16 activation domain. Finally, the incorporation of HMG17 into chromatin was found to increase the efficiency of transcription initiation, but not the extent of transcriptional elongation. Thus, HMG17 is a chromatin-specific transcriptional coactivator that increases the efficiency of initiation of transcription by RNA polymerase II.

show abstract

“…Thus, the N-terminal portion of the new protein contains three regions that are identical or highly homologous to regions known to be functionally relevant in HMG-14/-17 proteins. The first region of homology is part of the bipartite nuclear localization signal of HMG-14/-17 (19), the second region is their main nucleosomal binding domain (20), and the third region of homology is part of the chromatin unfolding domain (21,22). The calculated molecular mass of the protein is 45 kDa.…”

Section: Resultsmentioning

confidence: 99%

“…The only nuclear proteins known to recognize structural features of this chromatin subunit and bind to it specifically, independent of the underlying DNA sequence, are the ubiquitous HMG-14/-17 proteins. The main site of interaction between the HMG-14/-17 proteins and the nucleosome core particle is the highly conserved nucleosomal binding domain (20,26,27). Because a region of NBP-45 (amino acids 12-36; Fig.…”

Section: Nbp-45 Binds Specifically To Nucleosome Cores-mentioning

confidence: 99%

NBP-45, a Novel Nucleosomal Binding Protein with a Tissue-specific and Developmentally Regulated Expression

Shirakawa¹,

Landsman²,

Postnikov³

et al. 2000

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Here we characterize a novel murine nuclear protein, which we named NBP-45, that is related to the ubiquitous nuclear proteins HMG-14/-17, binds specifically to nucleosome core particles, and can function as a transcriptional activator. NBP-45 mRNA is expressed at low levels and in variable amounts in all mouse tissues tested but is especially abundant in RNA extracted from 7-day-old mouse embryos, suggesting that it functions in early embryonic development. NBP-45 is composed of 406 amino acids and is encoded by a single size transcript. The region spanning the N-terminal 85 amino acids contains three segments that are highly homologous to functionally important domains in the HMG-14/-17 protein family: the nuclear localization signal, the nucleosome binding domain, and the chromatin unfolding domain. The protein region spanning the C-terminal 321 amino acids has a 42% content of negatively charged residues. The first 23 amino acids contain a region necessary for nuclear entry of the protein, the region spanning residues 12-40 is the main nucleosomal binding domain of the protein, and the negatively charged, Cterminal domain is necessary for transcription activation. The functional domains of NBP-45 are indicative of a nuclear protein that binds to nucleosomes, thereby creating a chromatin region of high local negative charge. Our studies establish the nucleosomal binding domain as a protein motif that is present in other than just the ubiquitous HMG-14/-17 proteins. We suggest that the nucleosomal binding domain motif is a protein module that facilitates binding to nucleosomes in chromatin.In the cell nucleus, the orderly progression of many DNArelated activities, such as transcription, replication, recombination, and repair, are associated with changes in the higher order structure of the chromatin fiber and with a temporal disassembly of the nucleosome. These structural changes are facilitated by multiple types of reversible posttranslational modifications of the histones and by the activities of various multiprotein complexes that disrupt the histone-DNA interactions in nucleosomes (1-9). In addition, structural proteins that lack known enzymatic activity, such as the high mobility group (HMG) 1 proteins, are also known to modify the structure of their DNA binding site and induce an architecture that facilitates and enhances various DNA-related activities (10, 11). The HMG protein family is subdivided into three subfamilies: the HMG-1/-2 subfamily, the HMG-I/Y subfamily, and the HMG-14/-17 subfamily. Each of these subfamilies has a unique protein signature and a distinct functional motif. The HMG-1 domain is the functional domain of the HMG-1/-2 subfamily, the AT-hook is the functional domain of the HMG-I/Y family, and the nucleosomal binding domain is the functional motif of the HMG-14/-17 proteins. Through these domains the HMG proteins bind to their DNA or chromatin target, with little if any specificity for the underlying DNA sequence (10, 11).Two of the HMG functional domains, the HMG-1, and the AT-hoo...

show abstract

Nucleosome core binding region of chromosomal protein HMG-17 acts as an independent functional domain

Cited by 69 publications

References 21 publications

Architecture of the high mobility group nucleosomal protein 2-nucleosome complex as revealed by methyl-based NMR

Architecture of the high mobility group nucleosomal protein 2-nucleosome complex as revealed by methyl-based NMR

HMG17 is a chromatin-specific transcriptional coactivator that increases the efficiency of transcription initiation.

NBP-45, a Novel Nucleosomal Binding Protein with a Tissue-specific and Developmentally Regulated Expression

Contact Info

Product

Resources

About