Rosenfeld: Knock out wt Pit!, rescue using something called the SAF domain. Enhancers of Pit1 + catenin with matrin3n-network #AACR14
7:34pm April 5th 2014 via Hootsuite
Rosenfeld: Looking at Satb1, b-catenin enhancing transcription of Pit1, and its relation to matrin3 #AACR14
7:32pm April 5th 2014 via Hootsuite
Hearing G. Rosenfeld at #AACR14 reminds me how many super-bright people are working on transcription-factor regulation. True years ago &
7:31pm April 5th 2014 via Hootsuite
Rosenfeld: Nuclear architecture: "Fun to watch over the next few years". #AACR14
7:29pm April 5th 2014 via Hootsuite
Rosenfeld: Super enhancer concept: 212 / 821 not; but the eRNA level not particularly higher. #AACR14
7:27pm April 5th 2014 via Hootsuite
Rosenfeld: Same as with RAR, GATA3 is required. Sequential ChIP analysis shows co-recruitment of MegaTrans complex to enhancers #AACR14
7:26pm April 5th 2014 via Hootsuite
Rosenfeld: Mass-spec analysis of IP pulldown of RAR alpha: 2nd, GATA3 is recruited in trans to ER fn enhancer #AACR14
7:24pm April 5th 2014 via Hootsuite
Rosenfeld: Every enh (1000+) with ER, had RARalpha and RARgamma. Looking at in trans - protein-protein interaction #AACR14
7:23pm April 5th 2014 via Hootsuite
Rosenfeld: ER binds, brings in a complex (GATA3, c-Jun, c-Fos, many others); FOXA1 also the 'pioneer' #AACR14
7:22pm April 5th 2014 via Hootsuite
Rosenfeld: MegaTrans complex - present on active enhancers, not inactive ones #AACR14
7:21pm April 5th 2014 via Hootsuite
Rosenfeld: Knock down condensins - lower ER-regulated enhancers. How does it work? Other factors (HECTD1) recruited too #AACR14
7:20pm April 5th 2014 via Hootsuite
Rosenfeld: Looking at estrogen receptor and recruitment of condensins to enhancers #AACR14
7:19pm April 5th 2014 via Hootsuite
Rosenfeld:GRO-Seq and enhancer RNA; knocked-down eRNA req'd for both enhancer and coding gene transcription #AACR14
7:17pm April 5th 2014 via Hootsuite
Rosenfeld: H4R3me2(s) mark: a repressive mark, read by 7SK methylated xcript; JMJD6 disarms repression; pause released #AACR14
7:16pm April 5th 2014 via Hootsuite
Rosenfeld: Another type of enhancer, an 'anti-pause enhancer'. 1K identified Cell 2013 PubMed: http://t.co/djC2v1hZvK #AACR14
7:14pm April 5th 2014 via Hootsuite
Rosenfeld: But it appears that in stem cells - the enhancers are pre-marked to preclude premature enhancer:promoter looping #AACR14
7:13pm April 5th 2014 via Hootsuite
Rosenfeld: Are enhancers functional? Idea is that they are 'born' when several xf bind, signalling, ncRNA, H3K4me1 activate promoter #AACR14
7:12pm April 5th 2014 via Hootsuite
Rosenfeld: Enhancers we know little about. They are themselves transcription units. (Using GRO-seq in br ca cells) #AACR14
7:11pm April 5th 2014 via Hootsuite
Rosenfeld: Number of non-coding RNAs - many-fold greater than coding genes. >35K cis-acting; 6K trans. #AACR14
7:10pm April 5th 2014 via Hootsuite
Next up: M Geoff Rosenfeld, UCSD "Enhancer codes and eRNAs in regulation of gene transcriptional programs" #AACR14
7:09pm April 5th 2014 via Hootsuite
Slack:Q: 34 / let7 are families - look at other forms? A: 15 let-7's, at least 3 miR-34's. Let-7b and 34a for this study. #AACR14
7:08pm April 5th 2014 via Hootsuite
Slack:Q:Look at plasma miRNA? A: Didn't do that in this study #AACR14
7:07pm April 5th 2014 via Hootsuite
Slack: Result: a 44% survival benefit in their mouse model. Points to a post-doct talk tomorrow OASIS sched: http://t.co/PRaGogrRoK #AACR14
7:06pm April 5th 2014 via Hootsuite
Slack: Collaborator let them used an amphoteric liposome called a 'smarticle' to test. 7wk; showed miR-34 elevation in lung + blood #AACR14
7:02pm April 5th 2014 via Hootsuite
Slack: Both miR-34a and let-7b in combination - cell lines suggest synergistic effect for proliferation #AACR14
6:59pm April 5th 2014 via Hootsuite
Slack: Pre-treated with miR-34 - suppressed tumorigenesis. At 10 wk, then miR-34 introduced: tumors failed to progress #AACR14
6:57pm April 5th 2014 via Hootsuite
Slack: Looking at mice miRNA expression, all reduced levels in the mouse model. PubMed: http://t.co/HakgOcinmR #AACR14
6:56pm April 5th 2014 via Hootsuite
Slack: Uses a highly aggressive mouse model (Kras/G12D/+; p53fR172H/+). Poor responder model #AACR14
6:54pm April 5th 2014 via Hootsuite
Slack: let-7, miR-34: repress major oncogenes in lung cancer (RAS, MYC, BCL-2, EGFR); tumor suppressors (p53, RB, p53) [5-50%] #AACR14
6:53pm April 5th 2014 via Hootsuite
Slack: Targeting miRNAs via antisense one approach; another to target miRNA compl. site variants in 3' UTR's http://t.co/SLMpJgPoRy #AACR14
6:50pm April 5th 2014 via Hootsuite
Slack: Croce's data from Volinia et al PNAS 2006 PubMed: http://t.co/5W0crJdFui #AACR14
6:48pm April 5th 2014 via Hootsuite
Slack: Other history: 2002 miR-15/16 first ID'd as involved in carcinogenesis #AACR14
6:47pm April 5th 2014 via Hootsuite
Slack: Collaborating with Mirna Therapeutics. Another timeline 1993 lin-4, 2000 let-7 in human, 2013 first mimics being tested #AACR14
6:46pm April 5th 2014 via Hootsuite
Next up: Frank John Slack, Yale Univ "MicroRNA-based therapeutics in cancer" #AACR14
6:45pm April 5th 2014 via Hootsuite
He:Q: How a polycistronic RNA have different levels of exp? A: Differential processing by Drosha; also microRNA stability #AACR14
He:Q: c-Myc controls 35% of genes; why this miRNA? A: miR19 have mult. targets; but AKT up-regulated. miR-92: repress c-Myc #AACR14
6:42pm April 5th 2014 via Hootsuite
He: Evol history of miR-92 much broader, miR-17/18/20/19 only vertebrates. Unique functionality #AACR14 PubMed: http://t.co/PZOgaHm6mD
6:38pm April 5th 2014 via Hootsuite
He:Also shRNA Fbw7 knockdown shows effect. Cross-talk between oncogene c-Myc & tumor suppressor PI3K/AKT #AACR14
6:37pm April 5th 2014 via Hootsuite
He: miR-92 overexpression affects c-Myc dosage, discovered Fbw7 that miR-92 targets, show dependence #AACR14
6:35pm April 5th 2014 via Hootsuite
He: ID 19a-b component is critical for oncogenesis, along with c-myc. 19 / 92 have opposite effects in same cistron #AACR14
6:30pm April 5th 2014 via Hootsuite
He: Disfunctional 92 - similar accel. tumorigenesis, suggest not cooperative, but internal antagonistic components #AACR14
6:29pm April 5th 2014 via Hootsuite
He: mIR-17-92, mouse b-cell model; del. 92 component, stronger effect #AACR14
6:28pm April 5th 2014 via Hootsuite
He: Lessons from Lac operon - by analogy, working cooperatively perhaps? In mir-17-92 gives rise to six mature miRNAs; 3 families #AACR14
6:26pm April 5th 2014 via Hootsuite
He: Unique function: 50% miRNA precursors give rise to one product. 50% - polycistronic structure. Multiple targets, specificity #AACR14
6:25pm April 5th 2014 via Hootsuite
He: 2008 onward miRNA therapeutics in primates tested, from discovery in 1993. Today 2578 human miRNAs #AACR14
6:24pm April 5th 2014 via Hootsuite
Next up: Lin He, Univ CA Berkeley "Outside coding genome: MiRNAs make a big difference" #AACR14
6:22pm April 5th 2014 via Hootsuite
Educ Session: "Outside the Coding Genome: Non-Coding RNAs in the Oncogene and Tumor Suppressor Network" #AACR14
Kim: Nature Rev Genet article comparing engineered nucleases PubMed: http://t.co/BHdjA5jqaz showing success rates, target length #AACR14
6:00pm April 5th 2014 via Hootsuite
Kim: Two companies, ToolGen and Haplogen help with knockout cell panel in haploid cell lines #AACR14
5:59pm April 5th 2014 via Hootsuite
Kim: Also used ssODN - protein, guide RNA, and add'l oligonucleotide introducing rest. enzyme site #AACR14
5:58pm April 5th 2014 via Hootsuite
