The LDB1 Complex Co-opts CTCF for Erythroid Lineage-Specific Long-Range Enhancer Interactions

Lee, Jongjoo; Krivega, Ivan; Dale, Ryan K.; Dean, Ann

doi:10.1016/j.celrep.2017.05.072

Cited by 73 publications

(49 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…All three domains of CTCF may also interact with other proteins (see Fig. 1) (Chernukhin et al, 2007;Delgado-Olguín et al, 2012;Ishihara et al, 2006;Lee et al, 2017;Uusküla-Reimand et al, 2016;Xiao et al, 2011Xiao et al, , 2015 or RNA (Kung et al, 2015;Saldaña-Meyer et al, 2014;Sun et al, 2013), and are susceptible to post-translational modifications that could affect interactions with DNA or other proteins (Klenova et al, 2001;MacPherson et al, 2009;Yu et al, 2004).…”

Section: Ctcf Is Required For Early Vertebrate Developmentmentioning

confidence: 99%

Developing in 3D: the role of CTCF in cell differentiation

2018

View full text Add to dashboard Cite

CTCF is a highly conserved zinc-finger DNA-binding protein that mediates interactions between distant sequences in the genome. As a consequence, CTCF regulates enhancer-promoter interactions and contributes to the three-dimensional organization of the genome. Recent studies indicate that CTCF is developmentally regulated, suggesting that it plays a role in cell type-specific genome organization. Here, we review these studies and discuss how CTCF functions during the development of various cell and tissue types, ranging from embryonic stem cells and gametes, to neural, muscle and cardiac cells. We propose that the lineage-specific control of CTCF levels, and its partnership with lineage-specific transcription factors, allows for the control of cell type-specific gene expression via chromatin looping.

show abstract

Section: Ctcf Is Required For Early Vertebrate Developmentmentioning

confidence: 99%

Developing in 3D: the role of CTCF in cell differentiation

2018

View full text Add to dashboard Cite

show abstract

“…31 The LDB1 complex is the primary mediator of enhancer activity in erythroid cells through stabilization of contacts between globin and other erythroid genes and their enhancers. [42][43][44] ChIP indicated that BGLT3 is occupied by CBP/p300, which is enriched at enhancers, to the same extent as the HS2 enhancer in the b-globin LCR ( Figure 3A). H3K27ac, which marks both enhancers and promoters, was enriched at the g-globin promoters and within BGLT3 ( Figure 3B).…”

Section: Bglt3 Coding Sequences Have Enhancer Characteristicsmentioning

confidence: 99%

Fetal γ-globin genes are regulated by the BGLT3 long noncoding RNA locus

Ivaldi

Diaz

Chakalova

et al. 2018

Blood

Self Cite

View full text Add to dashboard Cite

Long noncoding RNAs (lncRNAs) are increasingly being appreciated as participants in regulation of important cellular processes, including transcription. Because lncRNAs are highly cell type specific, they have the potential to contribute to the unique transcriptional repertoire of diverse cells, but underlying mechanisms are unclear. We studied , an erythroid lncRNA encoded downstream ofγ-globin (). and γ-globin genes are dynamically cotranscribed in erythroid cells in vivo. Deletion of using CRISPR/Cas9 editing shows that it specifically contributes to regulation of γ-globin genes. We used reduction or overexpression of the RNA and inhibition of transcription through the locus by CRISPRi to distinguish functions of the transcript vs the underlying sequence. Transcription of the locus is critical for looping between the γ-globin genes and sequences. In contrast, the transcript is dispensable for γ-globin/ looping but interacts with the mediator complex on chromatin. Manipulation of the locus does not compromise γ-globin gene long-range looping interactions with the β-globin locus control region (LCR). These data reveal that regulates γ-globin transcription in a developmental stage-specific fashion together with the LCR by serving as a separate means to increase RNA Pol II density at the γ-globin promoters.

show abstract

“…Ultimately cohesin is removed from chromatin by WAPL (Busslinger et al, 2017; Gandhi et al, 2006; Haarhuis et al, 2017). In addition to these cell type invariant mechanisms, several recent studies have demonstrated a role for tissue-specific transcription factors in loop formation (Krivega et al, 2014; Lee et al, 2017; Song et al, 2007). While our knowledge regarding the general characteristics and mechanisms of loops is improving, much less is known regarding the scope, mechanisms, and functional significance of dynamic looping events during biological processes such as cellular differentiation.…”

Section: Introductionmentioning

confidence: 99%

Static and Dynamic DNA Loops form AP-1-Bound Activation Hubs during Macrophage Development

et al. 2017

View full text Add to dashboard Cite

SUMMARY The three-dimensional arrangement of the human genome comprises a complex network of structural and regulatory chromatin loops important for coordinating changes in transcription during human development. To better understand the mechanisms underlying context-specific 3D chromatin structure and transcription during cellular differentiation, we generated comprehensive in situ Hi-C maps of DNA loops in human monocytes and differentiated macrophages. We demonstrate that dynamic looping events are regulatory rather than structural in nature and uncover widespread coordination of dynamic enhancer activity at preformed and acquired DNA loops. Enhancer-bound loop formation and enhancer-activation of preformed loops together form multi-loop activation hubs at key macrophage genes. Activation hubs connect 3.4 enhancers per promoter and exhibit a strong enrichment for Activator Protein 1 (AP-1) binding events, suggesting multi-loop activation hubs involving cell-type specific transcription factors may represent an important class of regulatory chromatin structures for the spatiotemporal control of transcription.

show abstract

The LDB1 Complex Co-opts CTCF for Erythroid Lineage-Specific Long-Range Enhancer Interactions

Cited by 73 publications

References 63 publications

Developing in 3D: the role of CTCF in cell differentiation

Developing in 3D: the role of CTCF in cell differentiation

Fetal γ-globin genes are regulated by the BGLT3 long noncoding RNA locus

Static and Dynamic DNA Loops form AP-1-Bound Activation Hubs during Macrophage Development

Contact Info

Product

Resources

About