scholarly journals The LDB1 complex co-opts CTCF for erythroid lineage specific long-range enhancer interactions

2017 ◽  
Author(s):  
Jongjoo Lee ◽  
Ivan Krivega ◽  
Ryan K. Dale ◽  
Ann Dean
Keyword(s):  
Long Range ◽  
Gene Promoter ◽  
Gene Interactions ◽  
Substantial Fraction ◽  
Genome Wide ◽  
Long Range Interactions ◽  
Architectural Proteins ◽  
Enhancer Function ◽  
Restricted Pattern ◽  
Architectural Protein

SUMMARYLineage-specific transcription factors are critical for long-range enhancer interactions but direct or indirect contributions of architectural proteins such as CTCF to enhancer function remain less clear. The LDB1 complex mediates enhancer-gene interactions at the β-globin locus through LDB1 self-interaction. We find that a novel LDB1-bound enhancer upstream of carbonic anhydrase 2 (Car2) activates its expression by interacting directly with CTCF at the gene promoter. Both LDB1 and CTCF are required for enhancer-Car2 looping and the domain of LDB1 contacted by CTCF is necessary to rescue Car2 transcription in LDB1 deficient cells. Genome wide studies and CRISPR/Cas9 genome editing indicate that LDB1-CTCF enhancer looping underlies activation of a substantial fraction of erythroid genes. Our results provide a mechanism by which long-range interactions of architectural protein CTCF can be tailored to achieve a tissue-restricted pattern of chromatin loops and gene expression.

scholarly journals Architectural proteins Pita, Zw5,and ZIPIC contain homodimerization domain and support specific long-range interactions inDrosophila

2016 ◽  
pp. gkw371 ◽  
Author(s):  
Nikolay Zolotarev ◽  
Anna Fedotova ◽  
Olga Kyrchanova ◽  
Artem Bonchuk ◽  
Aleksey A. Penin ◽  
...  
Keyword(s):  
Long Range ◽  
Long Range Interactions ◽  
Architectural Proteins

scholarly journals Lineage-specific compaction of Tcrb requires a chromatin barrier to protect the function of a long-range tethering element

2014 ◽  
Vol 212 (1) ◽  
pp. 107-120 ◽  
Author(s):  
Kinjal Majumder ◽  
Olivia I. Koues ◽  
Elizabeth A.W. Chan ◽  
Katherine E. Kyle ◽  
Julie E. Horowitz ◽  
...  
Keyword(s):  
Long Range ◽  
Conformational Changes ◽  
Three Dimensional ◽  
Chromatin Conformation ◽  
Dynamic Changes ◽  
Architectural Elements ◽  
Receptor Locus ◽  
Long Range Interactions ◽  
Enhancer Function ◽  
Flanking Regions

Gene regulation relies on dynamic changes in three-dimensional chromatin conformation, which are shaped by composite regulatory and architectural elements. However, mechanisms that govern such conformational switches within chromosomal domains remain unknown. We identify a novel mechanism by which cis-elements promote long-range interactions, inducing conformational changes critical for diversification of the TCRβ antigen receptor locus (Tcrb). Association between distal Vβ gene segments and the highly expressed DβJβ clusters, termed the recombination center (RC), is independent of enhancer function and recruitment of V(D)J recombinase. Instead, we find that tissue-specific folding of Tcrb relies on two distinct architectural elements located upstream of the RC. The first, a CTCF-containing element, directly tethers distal portions of the Vβ array to the RC. The second element is a chromatin barrier that protects the tether from hyperactive RC chromatin. When the second element is removed, active RC chromatin spreads upstream, forcing the tether to serve as a new barrier. Acquisition of barrier function by the CTCF element disrupts contacts between distal Vβ gene segments and significantly alters Tcrb repertoires. Our findings reveal a separation of function for RC-flanking regions, in which anchors for long-range recombination must be cordoned off from hyperactive RC landscapes by chromatin barriers.

scholarly journals Exploring the mechanisms of genome-wide long-range interactions: interpreting chromosome organization

2016 ◽  
Vol 15 (5) ◽  
pp. 385-395 ◽  
Author(s):  
Jingjing Wang ◽  
Xianwen Meng ◽  
Hongjun Chen ◽  
Chunhui Yuan ◽  
Xue Li ◽  
...  
Keyword(s):  
Long Range ◽  
Chromosome Organization ◽  
Genome Wide ◽  
Long Range Interactions

scholarly journals Cohesin-dependent and independent mechanisms support chromosomal contacts between promoters and enhancers

2020 ◽  
Author(s):  
Michiel J. Thiecke ◽  
Gordana Wutz ◽  
Matthias Muhar ◽  
Wen Tang ◽  
Stephen Bevan ◽  
...  
Keyword(s):  
Steady State ◽  
Protein Degradation ◽  
Long Range ◽  
Transcriptional Control ◽  
Human Gene ◽  
Mechanistic Explanation ◽  
Interaction Partner ◽  
Gene Promoters ◽  
Architectural Proteins ◽  
Architectural Protein

AbstractIt is currently assumed that 3D chromosomal organisation plays a central role in transcriptional control. However, recent evidence shows that steady-state transcription of only a minority of genes is affected by depletion of architectural proteins such as cohesin and CTCF. Here, we have used Capture Hi-C to interrogate the dynamics of chromosomal contacts of all human gene promoters upon rapid architectural protein degradation. We show that promoter contacts lost in these conditions tend to be long-range, with at least one interaction partner localising in the vicinity of topologically associated domain (TAD) boundaries. In contrast, many shorter-range chromosomal contacts, particularly those that connect active promoters with each other and with active enhancers remain unaffected by cohesin and CTCF depletion. We demonstrate that the effects of cohesin depletion on nascent transcription can be explained by changes in the connectivity of their enhancers. Jointly, these results provide a mechanistic explanation to the limited, but consistent effects of cohesin and CTCF on steady-state transcription and point towards the existence of alternative enhancer-promoter pairing mechanisms that are independent of these proteins.

scholarly journals Constitutively bound CTCF sites maintain 3D chromatin architecture and long-range epigenetically regulated domains

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Amanda Khoury ◽  
Joanna Achinger-Kawecka ◽  
Saul A. Bert ◽  
Grady C. Smith ◽  
Hugh J. French ◽  
...  
Keyword(s):  
Long Range ◽  
Cell Types ◽  
Ctcf Binding ◽  
Chromatin Conformation ◽  
Cell Type ◽  
Chromatin Architecture ◽  
Topologically Associating Domain ◽  
Genome Wide ◽  
Domain Boundaries ◽  
Architectural Protein

AbstractThe architectural protein CTCF is a mediator of chromatin conformation, but how CTCF binding to DNA is orchestrated to maintain long-range gene expression is poorly understood. Here we perform RNAi knockdown to reduce CTCF levels and reveal a shared subset of CTCF-bound sites are robustly resistant to protein depletion. The ‘persistent’ CTCF sites are enriched at domain boundaries and chromatin loops constitutive to all cell types. CRISPR-Cas9 deletion of 2 persistent CTCF sites at the boundary between a long-range epigenetically active (LREA) and silenced (LRES) region, within the Kallikrein (KLK) locus, results in concordant activation of all 8 KLK genes within the LRES region. CTCF genome-wide depletion results in alteration in Topologically Associating Domain (TAD) structure, including the merging of TADs, whereas TAD boundaries are not altered where persistent sites are maintained. We propose that the subset of essential CTCF sites are involved in cell-type constitutive, higher order chromatin architecture.

scholarly journals Structural Changes in the Acceptor Site of Photosystem II upon Ca2+/Sr2+ Exchange in the Mn4CaO5 Cluster Site and the Possible Long-Range Interactions

Biomolecules ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. 371
Author(s):  
Koua
Keyword(s):  
Crystal Structure ◽  
Photosystem Ii ◽  
Long Range ◽  
Electron Acceptor ◽  
Structural Changes ◽  
Acceptor Site ◽  
Oxygen Evolving Complex ◽  
Long Range Interactions ◽  
Structural Perturbations ◽  
Oxygen Evolving

The Mn4CaO5 cluster site in the oxygen-evolving complex (OEC) of photosystem II (PSII) undergoes structural perturbations, such as those induced by Ca2+/Sr2+ exchanges or Ca/Mn removal. These changes have been known to induce long-range positive shifts (between +30 and +150 mV) in the redox potential of the primary quinone electron acceptor plastoquinone A (QA), which is located 40 Å from the OEC. To further investigate these effects, we reanalyzed the crystal structure of Sr-PSII resolved at 2.1 Å and compared it with the native Ca-PSII resolved at 1.9 Å. Here, we focus on the acceptor site and report the possible long-range interactions between the donor, Mn4Ca(Sr)O5 cluster, and acceptor sites.

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