# Histone Modification and Transcription Elongation in Human Cancer

> **NIH NIH R50** · NORTHWESTERN UNIVERSITY · 2020 · $185,418

## Abstract

Project Summary
The mixed lineage leukemia (MLL) gene was identified due to its involvement in chromosomal
translocations with a variety of translocation partners resulting in human acute myeloid or acute lymphoid
leukemia. Our purification of several of the translocation partners led to the identification of the Super
Elongation Complex (SEC), which includes the transcription elongation factors from the ELL family as well
as the RNA Polymerase II (Pol II) c-terminal domain kinase P-TEFb. One goal of this proposal is to identify
genes that are misregulated as a consequence of the chimeric protein recruiting SEC to MLL target genes,
which can result in loss of the transcription elongation checkpoint control and increased expression of
genes, contributing to oncogenesis. Identifying such genes could provide new therapeutic targets in the
treatment of these leukemias. Another goal is to elucidate the molecular mechanisms for the recruitment of
endogenous MLL as part of MLL/COMPASS and the MLL chimera/SEC to their sites on chromatin. We are
also investigating the regulation of the stability of endogenous MLL and how this regulation contributes to
leukemogenesis. Although MLL is frequently mutated in leukemia, the MLL3 and MLL4 branches of the
COMPASS family are frequently mutated in a large number of tumors. Since MLL3 and MLL4 COMPASS
regulate histone H3K4 monomethylation at transcriptional enhancers, we hypothesize that the loss of
MLL3/4 COMPASS function at enhancers contributes to misexpression of tumor suppressors or oncogenes.
Determining how these COMPASS mutations contribute to oncogenesis could lead to new strategies for
combating these cancers.

## Key facts

- **NIH application ID:** 9999316
- **Project number:** 5R50CA211428-05
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** EDWIN R SMITH
- **Activity code:** R50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $185,418
- **Award type:** 5
- **Project period:** 2016-09-19 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9999316

## Citation

> US National Institutes of Health, RePORTER application 9999316, Histone Modification and Transcription Elongation in Human Cancer (5R50CA211428-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9999316. Licensed CC0.

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