YY1 is indispensable for Lgr5
            <sup>+</sup>
            intestinal stem cell renewal

Perekatt, Ansu O.; Valdez, Michael J.; Davila, Melanie; Hoffman, Andrew R.; Bonder, Edward M.; Gao, Nan; Verzi, Michael P.

doi:10.1073/pnas.1400128111

Cited by 56 publications

(66 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similarly, YY1 was shown to regulate adipocyte differentiation, in that overexpression of YY1 in 3T3-L1 cells decreased differentiation and YY1 knockdown increased differentiation (58). More global gene expression analyses in cells from mice that conditionally deleted YY1 specifically in muscle cells, or in intestinal epithelial stem cells, indicated that the major pathways down-regulated in both types of knockout mice were mitochondrial bioenergetics pathways (59,60). The intestinal epithelial stem cells also revealed up-regulation of cell cycle genes, and ChIP-seq in these cells showed enrichment for RNA processing and mitochondrial functions.…”

Section: Discussionmentioning

confidence: 97%

YY1 plays an essential role at all stages of B-cell differentiation

Kleiman

Jia

Loguercio

et al. 2016

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

View full text Add to dashboard Cite

Ying Yang 1 (YY1) is a ubiquitously expressed transcription factor shown to be essential for pro-B-cell development. However, the role of YY1 in other B-cell populations has never been investigated. Recent bioinformatics analysis data have implicated YY1 in the germinal center (GC) B-cell transcriptional program. In accord with this prediction, we demonstrated that deletion of YY1 by Cγ1-Cre completely prevented differentiation of GC B cells and plasma cells. To determine if YY1 was also required for the differentiation of other B-cell populations, we deleted YY1 with CD19-Cre and found that all peripheral B-cell subsets, including B1 B cells, require YY1 for their differentiation. Transitional 1 (T1) B cells were the most dependent upon YY1, being sensitive to even a half-dosage of YY1 and also to short-term YY1 deletion by tamoxifen-induced Cre. We show that YY1 exerts its effects, in part, by promoting B-cell survival and proliferation. ChIP-sequencing shows that YY1 predominantly binds to promoters, and pathway analysis of the genes that bind YY1 show enrichment in ribosomal functions, mitochondrial functions such as bioenergetics, and functions related to transcription such as mRNA splicing. By RNA-sequencing analysis of differentially expressed genes, we demonstrated that YY1 normally activates genes involved in mitochondrial bioenergetics, whereas it normally down-regulates genes involved in transcription, mRNA splicing, NF-κB signaling pathways, the AP-1 transcription factor network, chromatin remodeling, cytokine signaling pathways, cell adhesion, and cell proliferation. Our results show the crucial role that YY1 plays in regulating broad general processes throughout all stages of B-cell differentiation.YY1 | B lymphocytes | differentiation | mitochondrial bioenergetics | transcription

show abstract

Section: Discussionmentioning

confidence: 97%

YY1 plays an essential role at all stages of B-cell differentiation

Kleiman

Jia

Loguercio

et al. 2016

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

View full text Add to dashboard Cite

show abstract

“…YY1 ChIP-seq peaks were obtained from a previous study that identified YY1 binding sites in adult intestinal epithelium (GSM1295000) (Perekatt et al, 2014). Genes within 30 kb regions of YY1 binding sites were overlapped with genes downregulated in intestinal epithelium upon YY1 loss (log 2 FC<−0.27 and Benjamini-Hochberg adjusted P<0.05, Table S1).…”

Section: Informatics Analysismentioning

confidence: 99%

“…YY1 also regulates mitochondrial genes, as it has been implicated in the maintenance of mitochondrial structure and function as well as in regulating oxidative phosphorylation and other ATP-yielding processes (Blattler et al, 2012;Perekatt et al, 2014). The molecular pathway through which YY1 acts to regulate these functions is unclear.…”

Section: Introductionmentioning

confidence: 99%

A YY1-dependent increase in aerobic metabolism is indispensable for intestinal organogenesis

et al. 2016

Self Cite

View full text Add to dashboard Cite

During late gestation, villi extend into the intestinal lumen to dramatically increase the surface area of the intestinal epithelium, preparing the gut for the neonatal diet. Incomplete development of the intestine is the most common gastrointestinal complication in neonates, but the causes are unclear. We provide evidence in mice that Yin Yang 1 (Yy1) is crucial for intestinal villus development. YY1 loss in the developing endoderm had no apparent consequences until late gestation, after which the intestine differentiated poorly and exhibited severely stunted villi. Transcriptome analysis revealed that YY1 is required for mitochondrial gene expression, and ultrastructural analysis confirmed compromised mitochondrial integrity in the mutant intestine. We found increased oxidative phosphorylation gene expression at the onset of villus elongation, suggesting that aerobic respiration might function as a regulator of villus growth. Mitochondrial inhibitors blocked villus growth in a fashion similar to Yy1 loss, thus further linking oxidative phosphorylation with late-gestation intestinal development. Interestingly, we find that necrotizing enterocolitis patients also exhibit decreased expression of oxidative phosphorylation genes. Our study highlights the still unappreciated role of metabolic regulation during organogenesis, and suggests that it might contribute to neonatal gastrointestinal disorders.

show abstract

“…As additional evidence that mitochondrial functions are significant in adult stem cell biology, the YY1 transcription factor, a regulator of nuclear genes encoding mitochondrial proteins, is required for intestinal stem cell renewal [60]. Mitochondrial DNA (mtDNA) mutations typical of oxidative damage arise frequently in intestinal stem cells [61], also suggesting a role for ROS generated by mitochondrial oxidative phosphorylation.…”

Section: Adult Stem Cellsmentioning

confidence: 99%