PREDICTED BEAF BINDING SEQUENCES IN D.MELANOGASTER:

Authors:
Eldon Emberly and Olivier Cuvier


USAGE:

The following links provide lists which will give links to launching GBROWSE, the genome browser. When the browser is first launched, scroll down to the 'Upload standard annotations' and click both boxes. Then click 'Update URLs'. This will then show all the known and predicted BEAF elements in the browser.

BEAF ELEMENTS DEFINED:
A BEAF element is a 200 bp sequence that contains at least 3 BEAF binding sites. There are 6709 BEAF elements in the Release 5 sequence of D.melanogaster genome. 1943 of these element have at lest 1 DREF binding site. In the browser, BEAF elements that contain a DREF site are flagged via a '_D' in the element label.

DUAL-CORE ELEMENTS DEFINED:
A DCORE = dual-core is composed of two BEAF element predictions separated by less than 800 bp. There are 479 predicted dual-core elements in the Release 5 genome.

DUAL-CORE LIKE ELEMENTS DEFINED:
We define a dual-core-like element to be one of the lone BEAF elements which have a neighbouring cluster of 2 CGATA's (in a 100 bp window) within 800 bp. There are 1169 such elements. The total set of dual-cores and dual-core-like elements gives 1648 elements.


PREDICTIONS & ANALYSIS:

Link to Release 3 Predictions/Results

DUAL-CORE BEAF ELEMENTS:
A statistically significant fraction of BEAF elements are found to be arranged in pairs. From BE76, BE28 and scs', the spacer sequence was found to be AT rich. Interestingly, these 'dual-core' elements are often found connected with a promoter of a gene with one BEAF element sitting over the promoter with the other sitting up-stream. Following from this finding is the tendency for these dual-core elements to sit between divergently spaced genes. Of the 6709 BEAF elements, 479 meet the criterion of being a dual-core element. The following links give access to these elements (the distances to the nearest neighbour  (NN) and next-nearest neighbour genes (NNN) are given):

Distribution of distances between dual-core and nearest promoter       - this graph highlights that most dual-cores reside nearby a promoter

LINK TO EXPERIMENTALLY KNOWN BEAF ELEMENTS:

List of known BEAF elements identified from the literature and unpublished experiments:                      Known BEAF elements

LINKS TO PREDICTONS:

dual-core elements in cdk7 locus

dual-core elements in mei-S332 locus

dual-core elements sorted by distance to nearest gene

dual-core elements sorted by combined NN and NNN distance

dual-core-like elemeents sorted by distance to nearest gene

dual-core-like elemeents sorted by distance to nearest gene


PROMOTER ANALYSIS:
Each promoter was analyzed to see if a prediction falls within a +/- 500 bp (1000 bp for dual-cores) of it.  For each set of predictions there is a link to the list of genes which have predictions in their promoters, and the GO analysis of these genes. For the GO analysis, the table is sorted by p-value. (Note: 'total' = # of genes with the given GO, 'hits' = # of genes with predictions in promoter, 'expect' = # of hits expected by chance). Clicking on a GO term will then take you to the list of named genes which fall into that class (genes which are just CG..., are not included in the gene list).

all BEAF promoters GO                  DCORE promoters GO                     DCORE-like promoters GO

BEAF only promoters GO               DREF promoters GO                     

SYNOPSIS: Gene Expression and GO Analysis highlight BEAF in cell-cycle and chromatin dynamics

*NOTES:
                a) all BEAF = predictions that contain 3 BEAF sites
                b) BEAF only =  predictions that contain 3 BEAF sites but NO DREF
                c) DREF = lone DREF elements (only one DREF site, no 3rd BEAF) and the BEAF elements that contain 1 DREF site
                d) DCORE =  dual-core elements made from the  BEAF predictions
                e) DCORE-like =  dual-core and dual-core-like elements

SUMMARY OF GO CORRELATIONS:

i) for BEAF/DCORE genes, their GO is related to ribosome, mRNA, chromatin, apoptosis, endocytosis, cell-cycle stuff and are underepresented for more complex biological processes like transport, nervous system stuff.
                        
ii) there is some separation of biological process for the BEAF only promoters compared to DREF promoters. BEAF promoters are involved in cell organization, chromosome stuff, and metabolism. DREF promoters are more directly involved in RNA processing. There are some shared common processes.

iii) During embryogenesis, there is no drastic changes in the relative expression of dref relative to that of beaf (Hart et al., 1999). On the contrary, only BEAF possesses the ability to bind dual-cores during mitosis, yet DREF is removed from chromatin at this stage. In the next G1 phase of the cell-cycle, the ability of DREF to competes for BEAF may thus be critical for expression of genes whose promoter overlap with dual-cores. In fact, BEAF elements containing DREF are highly enriched in GOs cell-cycle that are positively regulated. In contrast, DREF lone elements are not enriched in genes positively regulated through development that regulate cell-cycle, as most correspond to a BEAF dual-core. BEAF elements without DREF are also enriched in the GO cell-cycle for genes positively regulated. Therefore, dual-cores appear to be essential in the regulation of cell-cycle genes. However, while DREF may be required for their activation at the G1/S transition, the chromatin organization at dual-cores appear to be important to potentiate their activation.


GENE EXPRESSION DATA:
This is analysis of gene expression and the connection to BEAF/DREF elements. 

1) Link to all gene expression data plots for all genes in the drosophila genome: Plots of embryonic gene expression profiles

2) Correlation to BEAF expression: List of genes with BEAF dual-core in their promoter correlated and anti-correlated with BEAF expression.

3) Correlation to DREF expression: List of genes with DREF element in their promoter correlated and anti-correlated with DREF expression.


SUMMARY OF POSITIONAL CORRELATIONS:
Z score measures for various correlations between factors and genomic organization.

Factor-Function correlations:

BEAF
DCORE
Promoters
Z = 63.3
Z=22.83
Long Genes
Z=0.86
Z= -0.20
Voids
Z= -3.47
Z= -4.31
Gene Clusters
Z=10.30
Z=2.44

Factor-chromosome correlations:

BEAF
DCORE
X + Xh
Z = 14.4
Z = 10.7
2L+2R+2h
Z = -0.84
Z = -2.02
3L+3R+3h
Z = -4.59
Z = -2.97
4
Z = 4.80
Z = 0.19