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Epigenetic Modifications of Histones
Published in Cristina Camprubí, Joan Blanco, Epigenetics and Assisted Reproduction, 2018
George Rasti, Alejandro Vaquero
Evidence also suggests that histone methylation marks such as active H3K4me3 and inactive H3K9me3 are required in follicle and oocyte meiotic maturation (32,33). In Drosophila, the H3K9me3 HMTs dSETDB1/Eggless, SU (VAR)3-9, and dG9a, are very important regulators of oogenesis and are critical for fertility (34). Histone H2AK119 mono-ubiquitination by the polycomb repressive complex 1 (PRC1), and H3K27me3 by PRC2, also play a key role in repression of developmental genes to maintain ES cell identity (35,36). Moreover, H3K4 demethylation is, as in the case of spermatogenesis, critical for establishing DNA methylation imprinting during oogenesis. KDM1A or KDM1B are responsible for demethylating H3K4me1,me2 during oogenesis and preimplantation embryogenesis (37) (Table 2.1).
Genetics of mammalian meiosis
Published in C. Yan Cheng, Spermatogenesis, 2018
MAX, a partner of MYC family proteins, suppresses the expression of meiosis genes in embryonic stem cells and germline stem cells.8 Reduction of Max causes precocious meiotic entry in these stem cells in a Stra8-dependent manner, as evidenced by meiotic-like cytological changes, but not in fibroblasts. MAX is a component of an atypical polycomb repressive complex 1 (PRC1.6). Therefore, MAX represses meiosis genes in stem cells partly through the PRC1.6 complex.
Mechanisms of Fibril Formation and Cellular Response
Published in Martha Skinner, John L. Berk, Lawreen H. Connors, David C. Seldin, XIth International Symposium on Amyloidosis, 2007
Martha Skinner, John L. Berk, Lawreen H. Connors, David C. Seldin
including ones for post-translational protein processing (PDIA4, MAN1C1, MGAT2), ER and Golgi support (CLIMP-63), intracellular protein degradation (Cathepsin Z) and secretion (CAPDS2), while 22 genes met criteria in the L set, including ones for cytoskeletal (PRC1, MAP7, KPTN) and chromatin-related proteins (H2AFV, DERP6).
Novel chromobox 2 inhibitory peptide decreases tumor progression
Published in Expert Opinion on Therapeutic Targets, 2023
Lindsay W. Brubaker, Donald S. Backos, Vu T. Nguyen, Philip Reigan, Tomomi M Yamamoto, Elizabeth R. Woodruff, Ritsuko Iwanaga, Michael F. Wempe, Vijay Kumar, Christianne Persenaire, Zachary L. Watson, Benjamin G. Bitler
Polycomb Repressor Complex 1 and 2 (PRC1 and PRC2) are epigenetic complexes involved in chromatin-based gene regulation. Both PRC1 and PRC2 are essential for development and cellular differentiation. PRC1 specifically coordinates stemness and is critical in embryonic development [1,2]. The canonical PRC1 consists of four main subunits including Ring1A and Ring1B/2, chromobox (CBX 2,4,6,7, and 8), polycomb group ring finger protein (PCGF 1–6, PCGF4 is BMI1, PCGF2 is MEL18), and polyhomeotic-like protein (PHC 1, 2, and 3) [3]. It is understood that PRC1 activity is multifaceted, and its function is dependent on the complex composition. There are possibly greater than 60 different compositional profiles [4], and subunits of the PRC1 complex are aberrantly expressed in cancer and often serve an oncogenic role in driving cancer progression [5–7].
Beyond EZH2: is the polycomb protein CBX2 an emerging target for anti-cancer therapy?
Published in Expert Opinion on Therapeutic Targets, 2019
Maïka Jangal, Benjamin Lebeau, Michael Witcher
CBX members play a pivotal role in defining the genome-wide binding pattern of PRC1 complexes, thereby facilitating tissue specific, or stimuli specific, transcriptional regulation of distinct genes sets by PRC1. The heterogeneity of PRC1 components undoubtedly play an additional regulatory role affecting its activity and localization. For example, some CBX proteins are expressed in a tissue specific manner and these permutations between PRC1 members result in a variable efficiency and pattern of H2AK119ub and H3K27me3 placement [41]. Coupled with the variable affinity of CBX proteins for H3K27me3 or H3K9me3, the PRC1 complex is afforded a great deal of functional flexibility. Thus, CBX proteins play an important role in development, in the maintenance of the pluripotent state of stem cells and in cell fate decision.
The relationship between histone posttranslational modification and DNA damage signaling and repair
Published in International Journal of Radiation Biology, 2019
Ajit K Sharma, Michael J. Hendzel
Ubiquitylation of different sites on H2A have distinct physiological functions. We previously reported that the polycomb repressive complex 1 (PRC1) E3 ubiquitin ligase, which has an established role in ubiquitylation of histone H2A to promote transcriptional silencing, is also induced in response to DNA double-strand breaks (Ismail et al. 2010, 2012; Kakarougkas et al. 2014). Histone H2A ubiquitylation by PRC1 occurs on lysine 119 and is associated with transcriptional repression in the vicinity of the DSB. After DNA damage, transcriptional repression occurs up to several kilobases away from the DSB site in an ATM and H2AK119ub dependent manner (Shanbhag et al. 2010; Ismail et al. 2013; Kakarougkas et al. 2014) suggesting that it also silences transcription at DNA damage sites.