Constraints on the Hydropathicity and Sequence Composition of HCDR3 are Conserved Across Evolution

2002 ◽  
pp. 43-67 ◽  
Author(s):  
Jason Link ◽  
Ivaylo Ivanov ◽  
Gregory Ippolito ◽  
Harry Schroeder
Keyword(s):  
2021 ◽  
Vol 49 (7) ◽  
pp. 3856-3875
Author(s):  
Marina Kulik ◽  
Melissa Bothe ◽  
Gözde Kibar ◽  
Alisa Fuchs ◽  
Stefanie Schöne ◽  
...  

Abstract The glucocorticoid (GR) and androgen (AR) receptors execute unique functions in vivo, yet have nearly identical DNA binding specificities. To identify mechanisms that facilitate functional diversification among these transcription factor paralogs, we studied them in an equivalent cellular context. Analysis of chromatin and sequence suggest that divergent binding, and corresponding gene regulation, are driven by different abilities of AR and GR to interact with relatively inaccessible chromatin. Divergent genomic binding patterns can also be the result of subtle differences in DNA binding preference between AR and GR. Furthermore, the sequence composition of large regions (>10 kb) surrounding selectively occupied binding sites differs significantly, indicating a role for the sequence environment in guiding AR and GR to distinct binding sites. The comparison of binding sites that are shared shows that the specificity paradox can also be resolved by differences in the events that occur downstream of receptor binding. Specifically, shared binding sites display receptor-specific enhancer activity, cofactor recruitment and changes in histone modifications. Genomic deletion of shared binding sites demonstrates their contribution to directing receptor-specific gene regulation. Together, these data suggest that differences in genomic occupancy as well as divergence in the events that occur downstream of receptor binding direct functional diversification among transcription factor paralogs.


Mobile DNA ◽  
2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Pavel Jedlicka ◽  
Matej Lexa ◽  
Ivan Vanat ◽  
Roman Hobza ◽  
Eduard Kejnovsky

Abstract Background Nesting is common in LTR retrotransposons, especially in large genomes containing a high number of elements. Results We analyzed 12 plant genomes and obtained 1491 pairs of nested and original (pre-existing) LTR retrotransposons. We systematically analyzed mutual nesting of individual LTR retrotransposons and found that certain families, more often belonging to the Ty3/gypsy than Ty1/copia superfamilies, showed a higher nesting frequency as well as a higher preference for older copies of the same family (“autoinsertions”). Nested LTR retrotransposons were preferentially located in the 3’UTR of other LTR retrotransposons, while coding and regulatory regions (LTRs) are not commonly targeted. Insertions displayed a weak preference for palindromes and were associated with a strong positional pattern of higher predicted nucleosome occupancy. Deviation from randomness in target site choice was also found in 13,983 non-nested plant LTR retrotransposons. Conclusions We reveal that nesting of LTR retrotransposons is not random. Integration is correlated with sequence composition, secondary structure and the chromatin environment. Insertion into retrotransposon positions with a low negative impact on family fitness supports the concept of the genome being viewed as an ecosystem of various elements.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yousif M. Makeen ◽  
Xuanlong Shan ◽  
Habeeb A. Ayinla ◽  
Ekundayo Joseph Adepehin ◽  
Ndip Edwin Ayuk ◽  
...  

AbstractThe Zarga and Ghazal formations constitute important reservoirs across the Muglad Basin, Sudan. Nevertheless, the sedimentology and diagenesis of these reservoir intervals have hitherto received insignificant research attention. Detailed understanding of sedimentary facies and diagenesis could enhance geological and geophysical data for better exploration and production and minimize risks. In this study, subsurface reservoir cores representing the Zarga formation (1114.70–1118.50 m and 1118.50–1125.30 m), and the Ghazal formation (91,403.30–1406.83 m) were subjected to sedimentological (lithofacies and grain size), petrographic/mineralogic (thin section, XRD, SEM), and petrophysical (porosity and permeability) analyses to describe their reservoir quality, provenance, and depositional environments. Eight (8) different lithofacies, texturally characterized as moderately to well-sorted, and medium to coarse-grained, sub-feldspathic to feldspathic arenite were distinguished in the cored intervals. Mono-crystalline quartz (19.3–26.2%) predominated over polycrystalline quartz (2.6–13.8%), feldspar (6.6–10.3%), and mica (1.4–7.6%) being the most prominent constituent of the reservoir rocks. Provenance plot indicated the sediments were from a transitional continental provenance setting. The overall vertical sequence, composition, and internal sedimentary structures of the lithofacies suggest a fluvial-to-deltaic depositional environment for the Ghazal formation, while the Zarga formation indicated a dominant deltaic setting. Kaolinite occurs mainly as authigenic mineral, while carbonates quantitatively fluctuate with an insignificant amount of quartz overgrowths in most of the analyzed cores. Integration of XRD, SEM, and thin section analysis highlights that kaolinite, chlorite, illite, and smectite are present as authigenic minerals. Pore-destroying diagenetic processes (e.g. precipitation, cementation, and compaction etc.) generally prevailed over pore-enhancing processes (e.g. dissolution). Point-counted datasets indicate a better reservoir quality for the Ghazal formation (ɸ = 27.7% to 30.7%; K = 9.65 mD to 1196.71 mD) than the Zarga formation (17.9% to 24.5%; K = 1051.09 mD to 1090.45 mD).


2009 ◽  
Vol 25 (10) ◽  
pp. 1331-1332 ◽  
Author(s):  
M. Hamady ◽  
S. A. Wilson ◽  
J. Zaneveld ◽  
N. Sueoka ◽  
R. Knight

1998 ◽  
Vol 72 (11) ◽  
pp. 8502-8509 ◽  
Author(s):  
Ana Angulo ◽  
Martin Messerle ◽  
Ulrich H. Koszinowski ◽  
Peter Ghazal

ABSTRACT The cytomegalovirus (CMV) enhancer is a highly complex regulatory region containing multiple elements that interact with a variety of host-encoded transcription factors. Many of these sequence elements are conserved among the different species strains of CMV, although the arrangement of the various elements and overall sequence composition of the CMV enhancers differ remarkably. To delineate the importance of this region to a productive infection and to explore the possibility of generating a murine CMV (MCMV) under the control of human CMV (HCMV) genetic elements, the MCMV enhancer was resected and replaced either with nonregulatory sequences or with paralogous sequences from HCMV. The effects of these various deletions and substitutions on viral growth in transfected or infected tissue-culture cells were evaluated. We found that mutations in MCMV that eliminate or substitute for the enhancer with nonregulatory sequences showed a severe deficiency in virus synthesis. This growth defect is effectively complemented by the homologous MCMV enhancer as well as the HCMV enhancer. In the latter case, the chimeric viruses (hybrid MCMV strains) containing the molecularly shuffled human enhancer exhibit infectious kinetics similar to that of parental wild-type and wild-type revertant MCMV. These results also show that open reading frames m124, m124.1, and m125 located within the enhancer region are nonessential for growth of MCMV in cells. Most importantly, we conclude that the enhancer of MCMV is required for optimal infection and that its diverged human counterpart can advantageously replace its role in promoting viral infectivity.


2017 ◽  
Author(s):  
Pedro A. G. Tizei ◽  
Emma Harris ◽  
Marleen Renders ◽  
Vitor B. Pinheiro

AbstractInsertions and deletions (indels) are known to affect function, biophysical properties and substrate specificity of enzymes, and they play a central role in evolution. Despite such clear significance, this class of mutation remains an underexploited tool in protein engineering with no available platforms capable of systematically generating or analysing libraries of varying sequence composition and length. We present a novel DNA assembly platform (InDel assembly), based on cycles of endonuclease restriction and ligation of standardised dsDNA building blocks, that can generate libraries exploring both composition and sequence length variation. In addition, we developed a framework to analyse the output of selection from InDel-generated libraries, combining next generation sequencing and alignment-free strategies for sequence analysis. We demonstrate the approach by engineering the well-characterized TEM-1 β-lactamase Ω-loop, involved in substrate specificity, identifying multiple novel extended spectrum β-lactamases with loops of modified length and composition areas of the sequence space not previously explored. Together, the InDel assembly and analysis platforms provide an efficient route to engineer protein loops or linkers where sequence length and composition are both essential functional parameters.


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