PCGF3/5–PRC1 initiates Polycomb recruitment in X chromosome inactivation

Almeida, Mafalda; Pintacuda, Greta; Masui, Osamu; Koseki, Haruhiko; Gdula, Michal R.; Cerase, Andrea; Brown, David A.; Mould, Arne W.; Innocent, Cassandravictoria; Nakayama, Manabu; Schermelleh, Lothar; Nesterova, Tatyana B.; Brockdorff, Neil

doi:10.1126/science.aal2512

Cited by 225 publications

(312 citation statements)

References 33 publications

Supporting

Mentioning

274

Contrasting

Unclassified

Order By: Relevance

“…"Repeat A" binds proteins called SPEN and RBM15, and is required for the stabilization of spliced Xist RNA, and for Xist to silence actively transcribed regions of the X chromosome (Chu et al, 2015;Engreitz et al, 2013;Hoki et al, 2009;McHugh et al, 2015;Moindrot et al, 2015;Monfort et al, 2015;Patil et al, 2016;Royce-Tolland et al, 2010;Wutz et al, 2002). "Repeat B", and at least a portion of "Repeat C", bind HNRNPK to recruit the Polycomb Repressive Complex 1 (PRC1) to the inactive X chromosome (Almeida et al, 2017;Pintacuda et al, 2017). "Repeat E" binds many proteins, including CIZ1, and is required for the stable association of Xist with X-linked chromatin and for the sustained recruitment of Polycomb Repressive Complex 2 (PRC2) to the inactive X (Ridings-Figueroa et al, 2017;Smola et al, 2016;Sunwoo et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Non-linear sequence similarity between the Xist and Rsx long noncoding RNAs suggests shared functions of tandem repeat domains

Sprague

Waters

Kirk

et al. 2019

Preprint

View full text Add to dashboard Cite

The marsupial inactive X chromosome expresses a long noncoding RNA (lncRNA) called Rsx that has been proposed to be the functional analogue of eutherian Xist. Despite the possibility that Xist and Rsx encode related functions, the two lncRNAs harbor no linear sequence similarity.However, both lncRNAs harbor domains of tandemly repeated sequence. In Xist, these repeat domains are known to be critical for function. Using k-mer based comparison, we show that the repeat domains of Xist and Rsx unexpectedly partition into two major clusters that each harbor substantial levels of non-linear sequence similarity. Xist Repeats B, C and D were most similar to each other and to Rsx Repeat 1, whereas Xist Repeats A and E were most similar to each other and to Rsx Repeats 2, 3, and 4. Similarities at the level of k-mers corresponded to domain-specific enrichment of protein-binding motifs. Within individual domains, protein-binding motifs were often enriched to extreme levels. Our data support the hypothesis that Xist and Rsx encode similar functions through different spatial arrangements of functionally analogous protein-binding domains. We propose that the two clusters of repeat domains in Xist and Rsx function in part to cooperatively recruit PRC1 and PRC2 to chromatin. The physical manner in which these domains engage with protein cofactors may be just as critical to the function of the domains as the protein cofactors themselves. The general approaches we outline in this report should prove useful in the study of any set of RNAs.

show abstract

Section: Introductionmentioning

confidence: 99%

Non-linear sequence similarity between the Xist and Rsx long noncoding RNAs suggests shared functions of tandem repeat domains

Sprague

Waters

Kirk

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…In these cases, the survival of the single knockouts can be explained by functional compensation between the paralogs. For example, Pcgf3 −/− and Pcgf5 −/− single mutants are viable with no apparent phenotype [311]. However, Pcgf3 −/− and Pcgf5 −/− double mutant mice exhibit female-specific embryo lethality at mid-gestation, pinpointing the common functions of these two subunits in X chromosome inactivation [311].…”

Section: The Function Of Ncprc1 Subunits Are Often Essential For Mammmentioning

confidence: 99%

“…The closest relative of PCGF3 is PCGF5. The similar functions of the two paralogs (PCGF3 and PCGF5) in mouse embryonic development and in response to Xist RNA regulation has recently been established [311]. Almeida et al generated Pcgf3 −/− and Pcgf5 −/− single and double mutant ES cell lines, where Xist expression could be induced by doxycycline.…”

Section: Ncprc13 and Ncprc15mentioning

confidence: 99%

“…For example, Pcgf3 −/− and Pcgf5 −/− single mutants are viable with no apparent phenotype [311]. However, Pcgf3 −/− and Pcgf5 −/− double mutant mice exhibit female-specific embryo lethality at mid-gestation, pinpointing the common functions of these two subunits in X chromosome inactivation [311]. Since PCGF3 and PCGF5 are members of the ncPRC1s and not of the cPRCs, it is likely that ncPRCs have important functions in recruiting PcGs during X chromosome inactivation.…”

Section: The Function Of Ncprc1 Subunits Are Often Essential For Mammmentioning

confidence: 99%

“…Future studies will need to establish the nature of interaction between ncPRC1.3-ncPRC1.5 and corresponding region of Xist [311].…”

Section: The Function Of Ncprc1 Subunits Are Often Essential For Mammmentioning

confidence: 99%

See 2 more Smart Citations

From Flies to Mice: The Emerging Role of Non-Canonical PRC1 Members in Mammalian Development

2018

View full text Add to dashboard Cite

Originally two types of Polycomb Repressive Complexes (PRCs) were described, canonical PRC1 (cPRC1) and PRC2. Recently, a versatile set of complexes were identified and brought up several dilemmas in PRC mediated repression. These new class of complexes were named as non-canonical PRC1s (ncPRC1s). Both cPRC1s and ncPRC1s contain Ring finger protein (RING1, RNF2) and Polycomb group ring finger catalytic (PCGF) core, but in ncPRCs, RING and YY1 binding protein (RYBP), or YY1 associated factor 2 (YAF2), replaces the Chromobox (CBX) and Polyhomeotic (PHC) subunits found in cPRC1s. Additionally, ncPRC1 subunits can associate with versatile accessory proteins, which determine their functional specificity. Homozygous null mutations of the ncPRC members in mice are often lethal or cause infertility, which underlines their essential functions in mammalian development. In this review, we summarize the mouse knockout phenotypes of subunits of the six major ncPRCs. We highlight several aspects of their discovery from fly to mice and emerging role in target recognition, embryogenesis and cell-fate decision making. We gathered data from stem cell mediated in vitro differentiation assays and genetically engineered mouse models. Accumulating evidence suggests that ncPRC1s play profound role in mammalian embryogenesis by regulating gene expression during lineage specification of pluripotent stem cells.

show abstract

Male‐to‐female ratios among NTDs and women's periconceptional intake of folic acid

Shaw

Yang

Finnell

2020

Birth Defects Research

View full text Add to dashboard Cite

Background: About a decade ago, a hypothesis was put forward to explain the preponderance of females among neural tube defect (NTD) fetuses. That hypothesis predicts that a woman's higher levels of early gestational intake of methyl groups, such as folic acid, will be associated with lesser male-to-female ratio differences in NTD-affected births, specifically less preponderance of females. We explored this hypothesis in four distinct studies that investigated human NTDs, obtained information on folic acid, and capitalized on timing of folic acid fortification by investigating data that were collected both prior to and after the 1998 initiation of U.S. mandatory folic acid fortification of grains. Methods: We analyzed data from four population-based case control studies conducted in California for birth years spanning 1987-2011. Two studies were conducted before folic acid fortification of the U.S. food supply. Each of the four studies included interviews of women who either had NTD-affected pregnancies (cases) or who did not have a pregnancy affected by a birth defect (controls). In each study, information on periconceptional supplement use was elicited. We explored maleto-female ratios and 95% binomial confidence limits in each data set. Results: Our analyses of two case-control studies performed prior to and two performed post mandatory folate fortification in the United States showed that more NTD-affected fetuses were female in the first two studies. In the studies done before fortification, the frequency of females was even greater among those pregnancies without folic acid supplementation. Conclusion: Our findings suggest folic acid may differentially reduce risk of NTDs among female fetuses.

show abstract

PCGF3/5–PRC1 initiates Polycomb recruitment in X chromosome inactivation

Cited by 225 publications

References 33 publications

Non-linear sequence similarity between the Xist and Rsx long noncoding RNAs suggests shared functions of tandem repeat domains

Non-linear sequence similarity between the Xist and Rsx long noncoding RNAs suggests shared functions of tandem repeat domains

From Flies to Mice: The Emerging Role of Non-Canonical PRC1 Members in Mammalian Development

Male‐to‐female ratios among NTDs and women's periconceptional intake of folic acid

Contact Info

Product

Resources

About