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PCIF1 Catalyzes m6Am mRNA Methylation to Regulate Gene Expression

Journal Article

Summary mRNA modifications play important roles in regulating gene expression. One of the most abundant mRNA modifications is N6,2-O-dimethyladenosine (m6Am). Here, we demonstrate that m6Am is an evolutionarily conserved mRNA modification mediated by the...

The Histone Deacetylase SIRT6 Restrains Transcription Elongation via Promoter-Proximal Pausing

Journal Article

Transcriptional regulation in eukaryotes occurs at promoter-proximal regions wherein transcriptionally engaged RNA polymerase II (Pol II) pauses before proceeding toward productive elongation. The role of chromatin in pausing remains poorly understood...

RNA helicase DDX21 mediates nucleotide stress responses in neural crest and melanoma cells

Journal Article

The availability of nucleotides has a direct impact on transcription. The inhibition of dihydroorotate dehydrogenase (DHODH) with leflunomide impacts nucleotide pools by reducing pyrimidine levels. Leflunomide abrogates the effective transcription...

Transcription factor competition at the γ-globin promoters controls hemoglobin switching

Journal Article

BCL11A, the major regulator of fetal hemoglobin (HbF, α2γ2) level, represses γ-globin expression through direct promoter binding in adult erythroid cells in a switch to adult hemoglobin (HbA, α2β2). To uncover how BCL11A initiates repression, we used...

Balancing cohesin eviction and retention prevents aberrant chromosomal interactions, Polycomb-mediated repression, and X-inactivation

Journal Article

Depletion of architectural factors globally alters chromatin structure but only modestly affects gene expression. We revisit the structure-function relationship using the inactive X chromosome (Xi) as a model. We investigate cohesin imbalances by forcing...

Negative elongation factor regulates muscle progenitor expansion for efficient myofiber repair and stem cell pool repopulation

Journal Article

Negative elongation factor (NELF) is a critical transcriptional regulator that stabilizes paused RNA polymerase to permit rapid gene expression changes in response to environmental cues. Although NELF is essential for embryonic development, its role in...

A ubiquitous disordered protein interaction module orchestrates transcription elongation

Journal Article

Organized by unstructured motifs The high degree of conservation in protein sequences thought to be unstructured has hinted that these regions may have important biological functions. Although unstructured regions are widely viewed to be crucial for...

Rixosomal RNA degradation contributes to silencing of Polycomb target genes

Journal Article

Polycomb repressive complexes 1 and 2 (PRC1 and PRC2) are histone-modifying and -binding complexes that mediate the formation of facultative heterochromatin and are required for silencing of developmental genes and maintenance of cell fate . Multiple...

Screening thousands of transcribed coding and non-coding regions reveals sequence determinants of RNA polymerase II elongation potential

Journal Article

Precise regulation of transcription by RNA polymerase II (RNAPII) is critical for organismal growth and development. However, what determines whether an engaged RNAPII will synthesize a full-length transcript or terminate prematurely is poorly understood...

Mapping information-rich genotype-phenotype landscapes with genome-scale Perturb-seq

Journal Article

Summary A central goal of genetics is to define the relationships between genotypes and phenotypes. High-content phenotypic screens such as Perturb-seq (CRISPR-based screens with single-cell RNA-sequencing readouts) enable massively parallel functional...

Dynamic control of chromatin-associated m6A methylation regulates nascent RNA synthesis

Journal Article

Summary N6-methyladenosine (m6A) methylation is co-transcriptionally deposited on mRNA, but a possible role of m6A on transcription remains poorly understood. Here, we demonstrate that the METTL3/METTL14/WTAP m6A methyltransferase complex (MTC) is...

Overcoming IMiD resistance in T-cell lymphomas through potent degradation of ZFP91 and IKZF1

Journal Article

Immunomodulatory (IMiD) agents like lenalidomide and pomalidomide induce the recruitment of IKZF1 and other targets to the CRL4CRBN E3 ubiquitin ligase, resulting in their ubiquitination and degradation. These agents are highly active in B-cell lymphomas...