H2B Ubiquitylation Promotes RNA Pol II Processivity via PAF1 and pTEFb

Ling, Wu; Li, Li; Zhou, Bo; Qin, Zhaohui S.; Dou, Yali

doi:10.1016/j.molcel.2014.04.013

Cited by 81 publications

(94 citation statements)

References 66 publications

(102 reference statements)

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“…Mammals contain a similar MSL complex that is composed of orthologs of MSL1, MSL2, MSL3, and MOF and conducts H4K16 acetylation of all chromosomes (Smith et al 2005;Taipale et al 2005;Mendjan et al 2006;Wu et al 2014). Because of the high level of conservation in the sequences of CXC domain (a multiple sequence alignment can be found in Zheng et al 2012), its DNA-binding mode and even sequence specificity are likely conserved at the single-domain level.…”

Section: Discussionmentioning

confidence: 99%

Structural basis of X chromosome DNA recognition by the MSL2 CXC domain during Drosophila dosage compensation

et al. 2014

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The male-specific lethal dosage compensation complex (MSL-DCC) selectively assembles on the X chromosome in Drosophila males and activates gene transcription by twofold through histone acetylation. An MSL recognition element (MRE) sequence motif nucleates the initial MSL association, but how it is recognized remains unknown. Here, we identified the CXC domain of MSL2 specifically recognizing the MRE motif and determined its crystal structure bound to specific and nonspecific DNAs. The CXC domain primarily contacts one strand of DNA duplex and employs a single arginine to directly read out dinucleotide sequences from the minor groove. The arginine is flexible when bound to nonspecific sequences. The core region of the MRE motif harbors two binding sites on opposite strands that can cooperatively recruit a CXC dimer. Specific DNA-binding mutants of MSL2 are impaired in MRE binding and X chromosome localization in vivo. Our results reveal multiple dynamic DNA-binding modes of the CXC domain that target the MSL-DCC to X chromosomes.

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Section: Discussionmentioning

confidence: 99%

Structural basis of X chromosome DNA recognition by the MSL2 CXC domain during Drosophila dosage compensation

et al. 2014

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“…Protein extraction and Western blot analysis were performed as described previously (28). Insoluble chromatin fraction and soluble fraction were extracted according to the previous methods (30). Uncropped images of immunoblots are provided in Fig.…”

Section: Methodsmentioning

confidence: 99%

Nuclear Shp2 directs normal embryo implantation via facilitating the ERα tyrosine phosphorylation by the Src kinase

Hao

Kong

Zhang

et al. 2017

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

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Estrogen and progesterone coupled with locally produced signaling molecules are essential for embryo implantation. However, the hierarchical landscape of the molecular pathways that governs this process remains largely unexplored. Here we show that the protein tyrosine phosphatase Shp2, a positive transducer of RTK signaling, is predominately localized in the nuclei in the periimplantation mouse uterus. Uterine-specific deletion of Shp2 exhibits reduced progesterone receptor (PR) expression and progesterone resistance, which derails normal uterine receptivity, leading to complete implantation failure in mice. Notably, the PR expression defects are attributed to the limited estrogen receptor α (ERα) activation in uterine stroma. Further analysis reveals that nuclear Shp2, rather than cytosolic Shp2, promotes the ERα transcription activity. This function is achieved by enhancing the Src kinasemediated ERα tyrosine phosphorylation, which facilitates ERα binding to Pgr promoter in an ERK-independent manner in periimplantation uteri. Besides uncovering a regulatory mechanism, this study could be clinically relevant to dysfunctional ERα-caused endometrial disorders in women.Shp2 | ERK signaling | Src kinase | estrogen receptor | uterine receptivity S uccessful implantation requires synchronization between an implantation-competent blastocyst and a receptive uterus. In humans, natural conception per cycle is poor (∼30%), and ∼75% of failed pregnancies are considered to be due to implantation failure (1). One-third of implantation failure is attributed to the embryo itself, whereas the remaining two-thirds appear to result from inadequate uterine receptivity (2). The endometrium enters into a receptive stage for blastocyst implantation only in a restricted time period termed "implantation window," which is dominated by precisely regulated proliferation and differentiation of endometrial epithelium and stroma under the influence of progesterone and estrogen (3).Estrogen and progesterone bind to the estrogen receptor (ER) and progesterone receptor (PR), respectively, coupled with specific cofactors to endure the optimal functions. The activity of these nuclear receptors is also regulated at the posttranslational level by various modifications, such as phosphorylation, which can influence the protein stability, interaction with the cofactors and DNA binding affinity. So far, a wide range of nuclear receptor cofactors have been identified to ensure the normal ER transcriptional activation, such as the well-known steroid receptor coactivator (SRC) family members, which bind with ERα in the chromatin to recruit the histone acetyltransferase p300 (P300) for transcriptional activation (4-6). It is conceivable that ordered and combinatorial recruitment of cofactors at a specific target promoter after ERα binding to DNA sequence was essential to ensure target gene transcription. Recent evidence shows that nuclear receptor coactivator 6 is essential for embryo implantation by maintaining the appropriate level and activity of uteri...

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“…This implicates K27me1 as one of a suite of chromatin features that track with and/or accumulate in the wake of RNA polymerase II. Besides K36me3, similarly enriched co-transcriptional marks include H3-K79me2/3 and H2B-K120 mono-ubiquitylation (TANNY 2014;WU et al 2014). Although functions and interplay of these co-transcriptional modifications are not fully understood, key progress on this has emerged from studies in yeast (VENKATESH and WORKMAN 2015).…”

Section: K36me3 K27me1 and Chromatin Dynamics During Transcription mentioning

confidence: 99%

A Role for Monomethylation of Histone H3-K27 in Gene Activity inDrosophila

et al. 2018

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Polycomb repressive complex 2 (PRC2) is a conserved chromatin-modifying enzyme that methylates histone H3 on lysine-27 (K27). PRC2 can add one, two, or three methyl groups and the fully methylated product, H3-K27me3, is a hallmark of Polycomb-silenced chromatin.Less is known about functions of K27me1 and K27me2 and the dynamics of flux through these states. These modifications could serve mainly as intermediates to produce K27me3 or they could each convey distinct epigenetic information. To investigate this, we engineered a variant of Drosophila melanogaster PRC2 which is converted into a mono-methyltransferase.

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H2B Ubiquitylation Promotes RNA Pol II Processivity via PAF1 and pTEFb

Cited by 81 publications

References 66 publications

Structural basis of X chromosome DNA recognition by the MSL2 CXC domain during Drosophila dosage compensation

Structural basis of X chromosome DNA recognition by the MSL2 CXC domain during Drosophila dosage compensation

Nuclear Shp2 directs normal embryo implantation via facilitating the ERα tyrosine phosphorylation by the Src kinase

A Role for Monomethylation of Histone H3-K27 in Gene Activity inDrosophila

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